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.     

Cortical mechanisms mediating the inhibitory period after magnetic stimulation of the facial motor area

We studied the silent period (SP) that interrupts voluntary electromyographic activity (EMG) in facial muscles, after transcranial magnetic stimulation (TMS), in normal subjects. High-intensity magnetic stimulation with a 12-cm round coil centered at the vertex induced a long-lasting SP (215 ms), whereas supramaximal stimulation of the facial nerve only induced a short (< 20 ms) and incomplete EMG suppression, and cutaneous stimuli had no inhibitory effect at all. Cutaneous trigeminal stimulation delivered after TMS evoked blink-like reflexes, showing that facial motoneurons were not inhibited during the SP. Simultaneous recordings from perioral muscles (large cortical representation) and from orbicularis oculi and masseter muscles (small cortical representation) showed SPs of identical duration. Focal stimuli with a figure-of-eight coil showed that positioning of the coil was critical and that the optimal scalp sites for evoking the largest motor potentials and longest SPs coincided. Low-intensity stimulation occasionally elicited short SPs without a preceding motor potential. We conclude that the SP induced in facial muscles by TMS results from the excitation of cortical inhibitory interneurons surrounding the upper motoneurons. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 418–424, 1997.     

Trigemino-facial reflex inhibitory responses in some lower facial muscles

The effects of electrical trigeminal stimulation on activated facial muscles were studied in 20 normal subjects in order to evaluate whether excitatory or inhibitory responses are present and to investigate whether the reflex organization is similar in all the facial muscles. No inhibition was observed in frontalis, orbicularis oculi, orbicularis oris, and mentalis muscles. By contrast, a clear suppression of electromyographic (EMG) activity (late silent period or SP2) was present in the levator labii superioris, depressor anguli oris, and depressor labii inferioris muscles, with a mean latency ranging from 41.8 to 50.2 ms, and a mean duration ranging from 27.5 to 40.9 ms. An early suppression of EMG activity (early silent period or SP1) was observed, with a latency of 16 to 20 ms and a duration of 10 ms, mainly in inferior perioral muscles. Our findings show a selective trigeminal inhibitory influence upon some specific lower facial muscles.     

Speech-induced blepharospasm

Primary blepharospasm is an adult-onset dystonia typically present at rest and exacerbated by bright light, stress and voluntary movements of eyes and eyelids. Inconsistency or inducibility by activities involving muscles other than orbicularis oculi muscles are considered incongruous with typical primary blepharospasm, heralding the suspicion of psychogenicity. We report the clinical vignette of two patients manifesting an unusual presentation of primary blepharospasm, specifically triggered by voiced speech and associated with an otherwise ‘typical’ presentation of primary adult-onset dystonia in the lower face, larynx or upper limb. Speech-induced primary blepharospasm seems a rare occurrence, representing 1.3% of our clinic-based series of 149 patients with primary adult-onset primary blepharospasm. In these atypical patients, the feature of speech inducibility suggests that the abnormal surrounding inhibition between cortical subregions representing laryngeal and orbicularis oculi muscles might underlie dystonic overflow to the orbicularis oculi muscles following the voiced speech.     

Perioral reflexes in orofacial dyskinesia and spasmodic dysphonia.

In order to assess the clinical utility of trigemino-facial reflexes in lower facial muscles, we studied perioral reflexes to mechanical and electrical stimulation in 13 patients with spasmodic dysphonia and orofacial dyskinesia and in 7 healthy subjects. Mechanical stimulation of the upper lip of all patients and electrical stimulation of the infraorbital nerve of patients with orofacial dyskinesia elicited larger perioral reflexes than in controls. In the majority of patients, hyperexcitable perioral reflexes were accompanied by increased gain of the blink reflex. In 4 patients, however, trigemino-facial reflexes were enhanced selectively in either the perioral muscles or orbicularis oculi. Our findings suggest that the quantitative assessment of perioral reflexes may provide information about the excitability of brainstem interneurons in cranial dystonia that is complementary to blink reflex studies.     

Electromyography and recovery of the blink reflex in involuntary eyelid closure: a comparative study.

Electromyographic (EMG) activity of orbicularis oculi and levator palpebrae muscles was recorded to study the origin of involuntary eyelid closure in 33 patients. The evoked blink reflex in all patients and in 23 controls was also studied. To examine the excitability of facial motoneurons and bulbar interneurons in individual patients and to compare the results with EMG findings, R1 and R2 recovery indices were calculated in all subjects, as the average of recovery values at 0.5, 0.3, and 0.21 second interstimulus intervals. Based on EMG patterns, the patients were divided into three subclasses: EMG subclass 1, 10 patients with involuntary discharges solely in orbicularis oculi muscle; EMG subclass 2, 20 patients with involuntary discharges in orbicularis oculi and either involuntary levator palpebrae inhibition or a disturbed reciprocal innervation between orbicularis oculi and levator palpebrae; EMG subclass 3, three patients who did not have blepharospasm, but had involuntary levator palpebrae inhibition in association with a basal ganglia disease. The total patient group showed an enhanced recovery of both R1 and R2 components compared with controls. Although 30 out of 33 patients had blepharospasm (EMG subclasses 1 and 2), R1 recovery index was normal in 64% and R2 recovery index was normal in 54%. Patients with an abnormal R2 recovery index had an abnormal R1 recovery index significantly more often. All patients from EMG subclass 1 had an abnormal R2 recovery index, whereas all patients from EMG subclass 3 had normal recovery indices for both R1 and R2 responses. Seventy five per cent of the patients from EMG subclass 2 had normal recovery indices. The results provide further evidence that physiologically blepharospasm is not a homogeneous disease entity, and indicate that different pathophysiological mechanisms at the suprasegmental, or segmental level, or both are involved.     

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.     

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.     

Stretch reflex blepharospasm

We studied a patient with blepharospasm provoked by stretching the orbicularis oculi muscles. With the eyes closed, EMG of the orbicularis oculi at rest revealed spontaneous rhythmic muscle activity that was not visible. When she tried to open her eyes, repetitive jerking blepharoclonus and tonic blepharospasm rendered her functionally blind. Passive stretching of the orbicularis oculi evoked a burst of EMG activity with two components. Touch or pinprick did not elicit such reflex activity. Anesthesia of the supraorbital nerves abolished muscle responses to stretch and improved the blepharospasm.     

Silent period in upper limb muscles after noxious cutaneous stimulation in man

We studied the effect of electrical stimulation of the C5–C8 dermatomes on voluntary electromyographic activity (EMG) recorded from the ipsilateral first dorsal interosseus (FDI), abductor digiti minimi, flexor and extensor carpi, triceps brachii, biceps brachii, and orbicularis oculi muscles of healthy humans. Finger stimulation (C6–C8) produced an EMG inhibition (silent period, SP), which progressively decreased in duration from distal to proximal muscles; in the biceps it induced a slight facilitation and in the orbicularis oculi muscle, it had no effect. Stimulation of the C5 dermatome induced no response in either distal or proximal muscles. Only high-intensity stimuli evoked clear silent periods. The threshold for evoking and SP was almost double that required for sensory action potentials, 3.25 times the sensory threshold, and decidedly above the pain threshold. An indirect estimation of the conduction velocity of SP afferent fibres placed them in the A-delta group of myelinated fibres. In double-shock experiments, used to study the recovery cycle of the SP in the FDI muscle after finger stimulation, neither low- nor high-intensity conditioning stimuli delivered 100–500 ms before the test stimulus changed test SPs. Experiments designed to evaluate motoneuronal excitability showed that in relaxed FDI muscle, finger stimulation markedly reduced the F wave at the 50 ms time interval, the time when the SP normally occurs. Our findings demonstrate that the activation of A-delta afferents from the fingers inhibits the C7-T1 motoneurons postsynaptically, through an oligosynaptic spinal circuit. We propose that the strong inhibitory effect exerted by noxious cutaneous stimuli on all distal muscles may contribute to a defence action which is specific or the human upper limb.     

Neurophysiological observations on the effects of botulinum toxin treatment in patients with dystonic blepharospasm.

Botulinum toxin treatment improves dystonic blepharospasm by inducing transient paresis of the orbicularis oculi muscle. It is not known if it also reduces the enhanced brainstem neuronal excitability found in this disorder. We have performed conventional electromyography (EMG) and blink reflex excitability studies on fifteen patients with blepharospasm before and after botulinum toxin treatment. Denervation signs were found with needle EMG in all treated muscles. Amplitude of the facial compound muscle action potential (CMAP) and R1 response was reduced after botulinum toxin injections. In blink reflex excitability studies, the recovery of R2 response was enhanced after treatment even when patients were tested at the time of maximal benefit from botulinum toxin injections. The results suggest that there is little influence of botulinum toxin treatment upon the enhanced excitability of brainstem interneurons in patients with blepharospasm.     

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)     

Characterization of the facial expression of emotions in schizophrenia patients: preliminary findings with a new electromyography method.

OBJECTIVE: We investigated facial expression of emotions (FEE) in schizophrenia patients, using an improved and highly selective facial electromyography (EMG) method, and we examined the correlation between FEE and psychopathology. METHOD: We compared unmedicated patients with schizophrenia (n = 32) with healthy subjects (n = 21) with regard to the activity of 3 joy-relevant facial muscles (the M.zygomaticus, the M. orbicularis oculi, and the M.levator labii). Emotions were induced by pictures from the International Affective Picture System. We measured previsible muscle activity with a new, highly selective facial EMG. We used the Positive and Negative Syndrome Scale to evaluate psychopathology. RESULTS: Patients with schizophrenia showed fewer joy or smile reactions than did control subjects and displayed decreased activity of the M.orbicularis oculi and M.zygomaticus under presentation of positive pictures. Reduced activity of these muscles can be caused by depression. Increased activity of the M. levator labii correlates with positive symptoms. CONCLUSIONS: Our findings indicate that psychopathological syndromes correlate with schizophrenic mimic disturbances. These results can be used to compare various antipsychotics with regard to their influence on mimic disturbances.     

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.     

Quantitative EMG of facial muscles in myasthenia patients with MuSK antibodies.

OBJECTIVE: Our aim was to study the pathophysiological process leading to facial muscle atrophy in 13 patients with MuSK antibody positive myasthenia gravis (MuSK-MG), and to compare with findings from 12 acetylcholine receptor antibody positive myasthenia patients (AChR-MG), selected because they suffered from the same degree of disease severity and required similar treatment. METHODS: Motor unit action potential (MUAP) and interference pattern analysis from orbicularis oculi (O oculi) and orbicularis oris (O oris) muscles were studied using a concentric needle electrode, and compared with findings in 20 normal subjects, 6 patients receiving botulinum toxin injections (representing a neurogenic model) and 6 patients with a muscle dystrophy (representing a myopathic model). The techniques and control data have been reported previously. RESULTS: The mean MUAP durations for O oculi and O oris were significantly reduced (p<0.001) in both MG cohorts when compared with healthy subjects, and were similar to those in the myopathic control group. They were significantly different from those obtained from the neurogenic control group (p<0.001 for both O oculi and O oris). The MUAP findings in O oculi occurred independently from neuromuscular blocking on single fibre EMG (SFEMG) in the same muscle. On turns amplitude analysis (TAA), 50% of MuSK-MG patients and 42% of AChR-MG patients had a pattern in O oculi which was similar to that in the myopathic control group, and 62% of MuSK-MG patients and 50% of AChR-MG patients had a pattern in O oris that was also similar to that in the myopathic control group. The TAA findings for O oculi and O oris in both MG cohorts were different from those obtained from the neurogenic control group. CONCLUSIONS: Facial muscle atrophy in MuSK-MG patients is not neurogenic and the pathophysiological changes are akin to a myopathic process. The selected AChR-MG patients also show evidence of a similar pathophysiological process in the facial muscles albeit to a lesser degree. SIGNIFICANCE: We propose that muscle atrophy in MuSK-MG is a myopathic process consisting of either muscle fibre shrinkage or loss of muscle fibres from motor units. The duration of disease and long-term steroid treatment may be further contributory factors.     

Chewing pattern in patients with Meige's syndrome.

Meige's syndrome presents with a combination of upper and lower facial motor dysfunction, including eye closing spasms and oromandibular dystonia. While the pathophysiology of eye closing spasms has been extensively studied using the blink reflex and other trigeminofacial reflexes, very few studies have been carried out with regard to the abnormal perioral movements. We hypothesized that action-related dystonic features could be revealed by the analysis of the semiautomatic rhythmic movements required for chewing and swallowing. A total of 7 patients with Meige's syndrome that complained of chewing problems and 7 age-matched healthy volunteers were studied. Subjects were instructed to munch and swallow a small muffin while surface electromyographic (EMG) activity of masseter (MAS) and orbicularis oris (OOr) of the dominant side was recorded. In healthy subjects, MAS and OOr showed a rhythmic alternating phasic EMG pattern during chewing, which changed to a tonic cocontraction of both muscles during swallowing. Mean duration of MAS and OOr EMG bursts was, respectively, 297 +/- 28 msec and 328 +/- 29 msec. Patients exhibited the following alterations: excess duration of muscle activity, frequent cocontraction, loss of rhythmicity during chewing, and abnormalities in the chewing to swallowing transition phase. These abnormalities, similar in type to those encountered in other forms of focal dystonia, may be the expression of an abnormal motor control of basal ganglia over mastication-related movement pattern generators of the brainstem.     

Auditory startle reaction in primary blepharospasm.

Primary dystonia is associated with abnormal brainstem function, as shown by abnormalities of the blink reflex in blepharospasm (BSP) and of the auditory startle reaction in cervical dystonia. We examined the auditory startle reaction--a brainstem reflex elicited by an unexpected loud stimulus--in patients with primary BSP to expand knowledge on brainstem pathophysiology in primary focal dystonia. Thirteen patients with primary BSP were included and 13 age- and sex-matched healthy volunteers served as controls. Auditory startle responses (ASRs) were elicited by binaural high-intensity auditory stimuli, and reflex electromyographic activity was recorded simultaneously with surface electrodes bilaterally from masseter, orbicularis oculi, sternocleidomastoid, and biceps brachii muscles. Patients with BSP showed higher ASR probabilities (masseter, sternocleidomastoid, biceps brachii), shorter ASR onset latencies (masseter, orbicularis oculi, sternocleidomastoid), and larger ASR area-under-the-curve (masseter, sternocleidomastoid) as compared with normal controls. Habituation of ASRs did not differ significantly between patients and controls. These results corroborate previous findings of increased brainstem excitability in primary BSP but point to a different pattern of brainstem dysfunction compared to cervical dystonia, indicating that different pathophysiological mechanisms are involved in the two types of focal dystonia.     

Chondrodystrophic myotonia: electromyographic and cardiac features of a case

The Schwartz-Jampel syndrome or chondrodystrophic myotonia is a rare disease characterized by dwarfism, diffuse osteoarticular alterations, ble-pharospasm, perioral muscular contractions and electromyographic alterations. The authors present a case of chondrodystrophic myotonia focusing mainly on facial electromyographic and cardiac findings. The electromyo-graphy of the orbicularis oculi muscles showed abundant myotonic discharges like other facial muscles as well as muscles of the members. It was not possible to obtain true electrical silence between myotonic discharges, suggesting that the blepharospasm is a consequence of persistent muscular contraction. No conclusive evidence of myocardiopathy was given by clinical or laboratory cardiac examinations. General characteristics of the syndrome are discussed as well as the treatment with procamide and phenytoin.     

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.     

Quantitative ultrasonography of facial muscles

Introduction: There is no standardized method for examination of facial muscles with ultrasound. The purpose of this study was to identify those facial muscles accessible for reliable identification and to provide reference data. Methods: In healthy subjects all facial muscles were screened for visibility, separation from adjacent muscles, and reliability of landmarks. Bilateral scans of reliable muscles were performed in 40 adult volunteers. Results: Six facial muscles were clearly demarcated with ultrasound. These were: frontalis, orbicularis oculi, orbicularis oris, depressor anguli oris, depressor labii inferioris, and mentalis muscles. Cross-sectional area and muscle thickness showed gender differences and were independently related to age for some muscles. A significant left–right side difference was only seen for the orbicularis oculi muscle in women. Conclusions: These data demonstrate the usefulness of ultrasonography to assess facial muscles and provide reference values that can be applied in the clinical setting. Muscle Nerve 47: 878–883, 2013