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.     

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)     

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.     

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.     

Treatment with botulinum toxin improves the hyperexcitability of the facial motoneuron in patients with hemifacial spasm

Abstract

Botulinum toxin type A (BTX) injection into the orbicularis oculi muscle is an effective treatment for patients with hemifacial spasm (HFS). The objectives of this study were to investigate the effect of this treatment on HFS, in particular the associated hyperexcitability of the facial motor nucleus, and to discuss the potential mechanism of HFS. F waves in the mentalis muscle were examined before, 2 and 6 weeks after the BTX treatment of only the orbicularis oculi muscle in ten patients with HFS. F/M ratio, duration of F waves and frequency of F waves decreased significantly after the BTX treatment compared with those before the BTX treatment. These findings demonstrate that the excitability of the facial motonucleus decreases after BTX treatment of the orbicularis oculi muscle. From these results, we hypothesize that the trigeminal afferent input and the cortical control contribute to the hyperexcitability of the facial motor nucleus in patients with HFS. This warrants further investigation into the pathophysiology of HFS.     

Evaluation of proximal facial nerve conduction by transcranial magnetic stimulation.

A magnetic stimulator was used for direct transcutaneous stimulation of the intracranial portion of the facial nerve in 15 normal subjects and in patients with Bell's palsy, demyelinating neuropathy, traumatic facial palsy and pontine glioma. Compound muscle action potentials (CMAPs) thus elicited in the orbicularis oris muscle of controls were of similar amplitude but longer latency (1.3 SD 0.15 ms) compared with CMAPs produced by conventional electrical stimulation at the stylomastoid foramen. No response to magnetic stimulation could be recorded from the affected side in 15 of 16 patients with Bell's palsy. Serial studies in two patients demonstrated that the facial nerve remained inexcitable by magnetic stimulation despite marked improvement in clinical function. In the patient with a pontine glioma, the CMAP elicited by transcranial magnetic stimulation was of low amplitude but normal latency. In six of seven patients with demyelinating neuropathy, the response to intracranial magnetic stimulation was significantly delayed. Magnetic stimulation produced no response in either patient with traumatic facial palsy. Although the precise site of facial nerve stimulation is uncertain, evidence points to the labyrinthine segment of the facial canal as the most likely location.     

Prognostic value of minimal excitability of facial nerve in Bell's palsy.

Nerve excitability is useful for prognosis in Bell's palsy. Minimal excitability values (MEV) were obtained by stimulating the facial nerve and recording the effective current (mA) required to evoke a minimal visible contraction of frontalis, orbicularis oculi, orbicularis oris, and mentalis muscles respectively. Serial MEVs were performed on 100 patients with facial palsy, of whom 87 were followed for six months or to complete recovery; 61 patients were treated with steroids of whom 57 had good recovery. Serial MEVs were not only useful for prognosis, but also helpful in regulating the dosage of prednisone.     

The role of facial nerve conduction studies and electromyography in predicting the outcome of Bell's palsy

Many electrophysiological tests have been used to determine prognosis and extent of recovery in Bell's palsy but the reliability and sensitivity of the different parameters used is still controversial. We performed bilateral percutaneous facial nerve conduction studies, and volitional needle electromyography on 23 patients within 10–14 days post onset of their Bell's palsy. The following parameters were assessed: denervation and recruitment of the frontalis and orbicularis oris muscles, latency of the compound muscle action potential (CMAP), and CMAP amplitude ratio. The patients were re-examined 6 months later and their recovery graded according to the House-Brackman classification. The CMAP amplitude ratio and the recruitment scores of the frontalis and orbicularis oris muscles were the only parameters to reliably predict outcome (p = 0.016, 0.007 and 0.036, respectively). All patients with a CMAP amplitude ratio above 10% had a complete recovery. Since Bell's palsy is probably caused by herpes simplex virus, the active disease process is completed within 10–14 days; therefore, facial nerve conduction studies and electromyography at that time are appropriate to predict prognosis.     

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.     

Long-latency response to transcranial magnetic stimulation in patients with hemifacial spasm

Objective: We studied the long-latency response of the orbicularis oris muscle elicited with transcranial magnetic stimulation in patients with hemifacial spasm (HFS) and evaluated the excitability of the facial nucleus. Methods: We compared the thresholds on both sides in 8 normal volunteers and 7 patients with hemifacial spasm. The thresholds were determined as the lowest intensity required to produce motor evoked potentials with an amplitude of at least 50 μV in the orbicularis oris muscle. Average values were given as means±standard deviation. Wilcoxon's rank sum test was used for comparisons between the sides of normal subjects and of patients with HFS with respect to the threshold stimulus. Results: There was no significant difference between the thresholds on the two sides of the normal subjects (mean 1.88±5.30%, P>0.05). In patients with HFS, there was a significant difference between the thresholds on the spasm side and the normal side (mean 20.7±13.0%, P<0 05) In one patient studied after MVD, the difference between both sides disappeared. Conclusion: The difference between the thresholds in patients with HFS and the normalization in threshold after MVD suggested that the mechanism of HFS was hyperexcitability of the facial nucleus.     

Electrophysiological study of congenital facial paralysis

The common cause of neonatal facial asymmetry is facial nerve paralysis or "asymmetric crying facies syndrome". In the not uncommon later the lower lip, symmetrical at rest, becomes tilted to the so-called normal side when the patient is smiling or crying, as the congenital hypogenesis of sublabial muscles fail to pull down the lower lip in the opposite side. The electrophysiological differentiation between the two diseases has been performed by orbicularis oculi and oris reflexes with mechanically glabellar and supralabial tapping stimulation, respectively, in addition to needle and/or surface EMG recording. In the facial nerve paralysis of the case 1, R1 and R2 were absent in the orbicularis oculi and oris reflexes. EMG activity was completely lacking over the M. orbicularis oculi and oris innervated by facial nerve. On the contrary, the orbicularis oculi and oris reflexes were normal in the asymmetric crying facial of the case 2. EMG activity was absent only in the sublabial muscles including M. depressor anguli oris and/or M. depressor labii inferioris. Furthermore, needle EMG disclosed no spontaneous activity at rest, which was suggestive of no denervation in the sublabial muscles. It was, however, not possible to determine exactly which muscle the needle was inserted, the M. deprossor anguli oris or the M. depressor labii inferioris. The case 3 might be a variant of asymmetric crying facies with hypogenesis of M. orbicularis oris and/or oculi as well as the sublabial muscle, since the latency was normal but the amplitude was significantly attenuated in the components of orbicularis oculi and oris reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemifacial spasm as clinical presentation of intracranial meningiomas. Report of three cases and review of the literature

Hemifacial spasm (HFS) is a clinical entity consisting of brief clonic jerking movements of the facial musculature, beginning in the orbicularis oculi with downward spreading to other facial muscles. Apart from vascular loop compression at the root exit zone of the facial nerve, other causes of HFS are rare. It is exceptional as a form of presentation of intracranial meningiomas We report three cases of patients with meningiomas who presented with HFS, either as an isolated sign or associated with symptoms of rise intracranial pressure or focal deficit. We review the literature and discuss the possible physiopathological mechanisms responsible for this association.     

Abnormal muscle responses in hemifacial spasm: F waves or trigeminal reflexes?

OBJECTIVE: In patients with hemifacial spasm (HFS), abnormal muscle responses (AMR) are frequently present. The objective of this study was to investigate whether the afferent input of AMR is mediated by antidromic facial nerve stimulation or orthodromic trigeminal nerve stimulation. METHODS: AMR in the orbicularis oris muscle were recorded in 28 patients with HFS. When AMR were present, they were recorded after subthreshold stimulation of the facial nerve and weak stimulation delivered to the skin. RESULTS: AMR were recordable in 24 (86%) of the patients, and usually consisted of the early constant component (mean onset latency, 10.0 ms) and late variable component (35.3 ms), similar to R1 and R2 of the blink reflex. The early or late components of AMR, or both, were frequently elicited after subthreshold stimulation of the facial nerve (43%) and skin stimulation (88%). CONCLUSIONS: AMR are likely to be mediated by trigeminal afferent inputs, rather than antidromic activation of the facial nerve, and are a type of trigeminal reflex.     

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.     

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。     

Estimation of facial central motor delay by electrical stimulation of the motor cortex of the dog.

Central delay time (CD) has been estimated for activation of limb muscles by electrical or transcranial magnetic coil (TMC) stimulation of motor cortex and ventral root outflow. In the present study, we used surface electrical stimulation of the motor cortex of the right hemisphere to produce evoked compound muscle action potentials (CMAP) from the contralateral orbicularis oris (o.r.), and orbicularis oculi (o.c.), in dogs. Monopolar electrical stimulation of the facial nerve at the cerebello-pontine (CP) angle yielded CMAP activation of ipsilateral facial muscles. These latencies when subtracted from those obtained by direct cortical stimulation established CD for activation of the seventh cranial nerve. Preliminary data with single pulse magnetic stimulation at high outputs (greater than 80%) revealed CMAP with onset latencies similar to the direct facial nerve stimulation at the CP angle by electrical means.     

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.     

Pathophysiology of hemifacial spasm: II. Lateral spread of the supraorbital nerve reflex

The blink reflex was examined in 62 patients with hemifacial spasm. The latency and amplitude of the early (R-1) component of the orbicularis oculi response were increased as compared with the contralateral, unaffected side and controls, p less than 0.001. On the affected side, all patients showed a synkinetic response in the mental muscle, and after-activity and late-activity was observed after the reflex response. These findings indicate lateral spread of impulses to other fibers in the facial nerve (ephaptic transmission) and autoexcitation of fibers. The increased latency indicates a slowing of the nerve conduction in the facial nerve, in keeping with pathologic findings of focal demyelination.     

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.