Interaction between the blink reflex and the abnormal muscle response in patients with hemifacial spasm: results of intraoperative recordings

Patients with hemifacial spasm (HFS) have an abnormal muscle response (AMR) that can be elicited by stimulating one branch of the facial nerve and recording electromyographically from muscles innervated by other branches of the facial nerve. In addition, the R1 component of the blink reflex can be elicited from the affected side in patients with HFS who are undergoing microvascular decompression (MVD) operations under inhalation anesthesia. A synkinetic component of the blink reflex response that corresponds to the R1 component can be recorded from the mentalis muscle. In the present study we show that the blink reflex elicited by electrical stimulation of the supraorbital nerve can suppress the AMR elicited by electrical stimulation of the temporal branch of the facial nerve in patients with HFS when the interval between stimulation of the supraorbital nerve and stimulation of the temporal branch of the facial nerve (interstimulus interval, ISI) is such that the blink reflex response would appear later than the AMR if they had been elicited independently. Within a short range of ISIs the two responses suppress each other partially or totally. We find evidence that the suppression of the AMR is the result of an interaction in the facial motonucleus. We believe that the results of the present study support the hypothesis that the facial motonucleus is hyperactive in patients with HFS, and we suggest that the AMR is a result of backfiring from the facial motonucleus and that it may thus be an exaggerated F-response.     

Physiological abnormalities in hemifacial spasm studied during microvascular decompression operations

The pathophysiology of hemifacial spasm was studied using electrophysiologic recordings made during neurosurgical operations to relieve it by microvascular decompression of the facial nerve near its entrance into the brain stem. Electrical stimulation of the temporal or the marginal mandibular branch of the facial nerve resulted in a response not only from the muscles that were innervated by the branch of the facial nerve that was stimulated, but also from other muscles, as evidenced by EMG recordings. This "lateral spread" of antidromic activity was facilitated by stimulation at a high rate (50 pps): the response increased five- to tenfold within a few seconds. When the repetition rate was reduced to the initial low stimulus rate (2 to 5 pps), facilitation continued for periods lasting from a few seconds to several minutes. The amplitude of the response of the supraorbital reflex (blink reflex), which can be elicited in patients with hemifacial spasm intraoperatively on the affected side despite the use of inhalation anesthesia, also increased after brief stimulation at a high rate (50 pps). After the facial nerve had been decompressed, both the lateral spread response and the blink reflex response were absent. These results support the hypothesis that hemifacial spasm is the result of hyperexcitability of the facial motor nucleus and facilitation of cross-transmissions between cells in the nucleus that innervate different parts of the face.     

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.     

Reflexes elicited from cutaneous and mucosal trigeminal afferents in normal human subjects

It has been shown that in patients in whom the central stump of the hypoglossal nerve has been anastomosed to the peripheral stump of a lesioned facial nerve, supraorbital nerve stimulation can elicit a short-latency reflex (12.5±0.6 ms; mean±S.D.) in facial muscles similar to the R1 disynaptic blink reflex response, but not followed by an R2 blink reflex component⁴⁶. Thus in addition to replacing the facial neurons at peripheral synapses, these hypoglossal nerves contribute to a trigemino-hypoglossal reflex. The aim of this work was to study the type of reflex activities which can be elicited in both facial and tongue muscles by electrical stimulation of cutaneous (supraorbital nerve) or mucosal (lingual nerve) trigeminal (V) afferents in normal subjects. The results show that although stimulation of cutaneous V1 afferents elicits the well-known double component (R1–R2) blink reflex response in the orbicularis oculi muscles, it does not produce any detectable reflex response in the genioglossus muscle, even during experimental paradigms designed to facilitate the reflex activity. Conversely, stimulation of mucosal V3 afferents can elicit a single reflex response of the R1 type in the genioglossus muscle but not in the orbicularis oculi muscles, even during experimental paradigms designed to facilitate the reflex activity. These data are discussed in terms of two similar but separate circuits for the R1 responses of cutaneous (blink reflex) and mucosal (tongue reflex) origins. They suggest that in patients with hypoglossal-facial (XII–VII) nerve anastomosis, the short-latency trigemino-‘hypoglossal-facial' reflex of the R1 blink reflex type observed in facial muscles following supraorbital nerve stimulation could be due to changes in synaptic effectiveness of the central connectivity within the principal trigeminal nucleus where both cutaneous and mucosal trigeminal afferents project.     

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.     

Unmasking of the trigemino-accessory reflex in accessory facial anastomosis

OBJECTIVE: To evaluate the possible blink reflex responses in facial muscles reinnervated by the accessory nerve. METHOD: Eleven patients with a complete facial palsy were submitted to a surgical repair by an accessory facial nerve anastomosis (AFA). In this pathological group, blink reflex was studied by means of percutaneous electrical stimulation of the supraorbital nerve and recording from the orbicularis oculi muscle. A control group comprised seven normal people and seven patients with a complete Bell's facial palsy; in this group, responses on the sternocleidomastoideus (SCM) muscles were studied after supraorbital nerve stimulation. RESULTS: All the patients with AFA showed a consistent degree of facial reinnervation. Ten out of the 11 patients with AFA showed reflex responses; in six, responses were configured by a double component pattern, resembling the R1 and R2 components of the blink reflex; three patients had an R1-like response and one patient showed a unique R2 component. Mean values of latencies were 15.2 (SD 4.6) ms for the R1 and 85.3 (SD 9.6) ms for the R2. In the control group, eight out of 14 people had evidence of reflex responses in the SCM muscles; these were almost exclusively configured by a bilateral late component (mean latency 63.5 (SD15.9) ms) and only one of the subjects showed an early response at 11 ms. CONCLUSION: The trigemino-accessory reflex response in the pathological group was more complex and of a significantly higher incidence than in the control group. These differences could be tentatively explained by a mechanism of synaptic plasticity induced by the impairment of the efferent portion of the reflex. This could unmask the central linking between the trigeminal and the accessory limbs of the reflex. The findings described could be a demonstration of neurobionomic function in the repairing process of the nervous system.     

Further evidence for a central reorganisation of synaptic connectivity in patients with hypoglossal-facial anastomosis in man

In normal subjects, electrical stimulation of trigeminal mucosal afferents (lingual nerve - V3) can elicit a short latency (12.5+/-0. 3 ms; mean+/-S.D.) reflex response in the ipsilateral genioglossus muscle (Maisonobe et al., Reflexes elicited from cutaneous and mucosal trigeminal afferents in normal human subjects. Brain Res. 1998;810:220-228). In the present study on patients with hypoglossal-facial (XII-VII) nerve anastomoses, we were able to record similar R1-type blink reflex responses in the orbicularis oculi muscles, following stimulation of either supraorbital nerve (V1) or lingual nerve (V3) afferents. However, these responses were not present in normal control subjects. Voluntary swallowing movements produced clear-cut facilitations of the R1 blink reflex response elicited by stimulation of V1 afferents. In a conditioning-test procedure with a variable inter-stimulus interval, the R1 blink reflex response elicited by supraorbital nerve stimulation was facilitated by an ipsilateral mucosal conditioning stimulus in the V3 region. This facilitatory effect was maximal when the two stimuli (conditioning and test) were applied simultaneously. This effect was not observed on the R1 component of the blink reflex in the normal control subjects. These data strongly suggest that in patients with XII-VII anastomoses, but not in normal subjects, both cutaneous (V1) and mucosal (V3) trigeminal afferents project onto the same interneurones in the trigeminal principal sensory nucleus. This clearly supports the idea that peripheral manipulation of the VIIth and the XIIth nerves induces a plastic change within this nucleus.     

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.     

Long latency response of the mentalis muscle following transcranial magnetic stimulation with a circular coil in normal subjects

Short latency response (SLR), middle latency response and long latency response (LLR) are elicited in facial muscles by transcranial magnetic stimulation. Although it has been said that the LLRs are elicited by the trigeminal nerve stimulation, a trigeminofacial reflex is recorded easily in normal subjects by the electrical stimulation in orbicularis oculi muscles as a blind reflex, but a trigeminal-facial reflex recorded in orbicularis oris, namely a snout reflex, is more difficult to record in normal subjects. The aim of this study is to demonstrate the LLR of lower facial muscles (mentalis muscle) by the transcranial magnetic stimulation, using a circular coil. The transcranial magnetic stimulations were performed over parieto-occipital scalp with frequencies of random and 0.3 Hz in 11 normal subjects and the responses in the mentalis muscle were recorded. The LLR of the mentalis muscle was recorded in all 11 subjects following SLRs. The latency, duration and LLR/SLR ratio were 37.4 msec, 20.3 msec and 9.1%, respectively. The waveform of the LLR varied trial to trial showing habituation with a stimulation of 0.3 Hz. At this time the LLR of the masseter muscle was not recorded following this transmagnetic stimulation. It was suggested that the LLR of the mentalis muscle is recorded by the transcranial magnetic stimulation of the trigeminal nerve with a circular coil. The ease and reliability of their recording make it possible to apply this LLR clinically as well as a blink reflex.     

Neurophysiological evaluation of trigeminal and facial nerves in patients with chronic inflammatory demyelinating polyneuropathy

Cranial neuropathy is clinically uncommon in patients with chronic inflammatory demyelinating polyneuropathy (CIDP), but there is little information on the neurophysiological examination of cranial nerve involvement. To determine the incidence of trigeminal and facial nerve involvement in patients with CIDP, the direct response of the orbicularis oculi muscle to percutaneous electric stimulation of the facial nerve and the blink reflex (induced by stimulation of the supraorbital nerve) were examined in 20 CIDP patients. The latency of the direct response was increased in 12 patients (60%) and an abnormal blink reflex was observed in 17 patients (85%). There was no correlation between electrophysiological findings and the latencies of the direct and R1 responses and disease duration or clinical grade in CIDP patients. Nevertheless, the prevalence of subclinical trigeminal and facial neuropathy is extremely high in patients with CIDP when examined by neurophysiological tests.     

Axon reflexes or ephaptic responses simulating blink reflex R1 after XII-VII nerve anastomosis

It has been claimed that functional recovery of the blink reflex occurs after hypoglossal-facial nerve anastomosis. This has been explained through central nervous system plasticity and reorganization of neuronal connections. In 5 patients with reinnervated facial muscles after hypoglossal-facial nerve anastomosis, we observed “R1-like” responses that fulfilled criteria for facial nerve axon reflexes or ephapses. First, displacement of the stimulating electrode from the supraorbital to the zygomatic area shortened the latency of the evoked response. Second, these responses were stable (jitter mean consecutive difference < 25 μs) and they had complex potential shapes unmodified by high-frequency stimulation. Finally, collision techniques demonstrated antidromic conduction of impulses in the facial nerve from supraorbital to zygomatic points. Therefore, these “R1-like” responses are not the early component of a functionally recovered blink reflex but motor axon reflexes or ephaptic responses similar to the short latency responses observed following facial nerve regeneration or from sutured nerves in human forearms. © 1996 John Wiley & Sons, Inc.     

Acute migraine headache: possible sensitization of neurons in the spinal trigeminal nucleus?

OBJECTIVE: To investigate trigeminal sensory processing in patients with migraine using a novel "nociception-specific" blink reflex. METHODS: Seventeen patients with unilateral migraine headache were studied within 6 hours of onset. Blink reflexes were elicited with a standard stimulating electrode (standard blink reflex) and concentric stimulating electrode (nociception-specific blink reflex) during the acute migraine attack, after treatment with IV lysine acetylsalicylate (1,000 mg) or oral zolmitriptan (5 mg) and interictally. RESULTS: After standard stimulation, no differences were detected for the R1 and R2 onset latencies and areas under the curve (AUC) between the different time points and the headache and nonheadache side. Nociception-specific stimulation revealed a shortening of R2 onset latencies (44.3 +/- 5.4 ms for headache side vs 48.9 +/- 5.8 ms for nonheadache side) during the acute migraine attack compared with the headache-free interval (49.8 +/- 5.3 vs 49.8 +/- 4.5 ms). The AUC of the R2 increased on the headache side by 680% and on the nonheadache side by 230% compared with the headache-free interval. Drug treatment parallel to pain relief increased the onset latencies (zolmitriptan: 48.0 +/- 8.2 ms for headache side vs 52.3 +/- 7.6 ms for nonheadache side; lysine acetylsalicylate: 48.0 +/- 5.0 ms for headache side vs 51.2 +/- 5.6 ms for nonheadache side) and reduced the AUC of R2 (zolmitriptan by 45% and lysine acetylsalicylate by 48%). CONCLUSION: The data suggest temporary sensitization of central trigeminal neurons during acute migraine attacks.     

Cortical control of voluntary blinking: a transcranial magnetic stimulation study.

OBJECTIVE: To investigate cortical regions related to voluntary blinking. METHODS: Transcranial magnetic stimulation (TMS) was applied to the facial motor cortex (M1) and the midline frontal region (Fz) in 10 healthy subjects with eyes opened and closed. Motor-evoked potentials were recorded from the orbicularis oculi (OOC), orbicularis oris (OOR), abductor digiti minimi and tibialis anterior using surface and needle electromyography electrodes. Facial M waves and blink reflex were measured using supramaximal electrical stimulation of the facial and supraorbital nerves. RESULTS: TMS at Fz elicited 3 waves in OOC with no response in other tested muscles except for the early wave in OOR. Facial M1 stimulation produced only early and late waves. Because of their latencies, shapes, and relationship to coil position and stimulation intensity, early and late waves appeared to be analogous to the facial M wave and R1 component of the blink reflex. The intermediate wave at 6-8 ms latency was elicited in OOC by Fz stimulation with eyes closed. CONCLUSIONS: Since its latency matches the central conduction time of other cranial muscles and it has characteristic of muscle activation-related facilitation, the intermediate wave is presumably related to cortical stimulation. This result provides evidence that the cortical center for the upper facial movements, including blinking, is not principally located in the facial M1, but rather in the mesial frontal region.     

Contralateral reinnervation in Bell's palsy. A case report.

Congenital lesion of the left facial nerve trunk has been investigated in a 30-year-old woman. Upon stimulation of the left facial nerve, no response was evoked in any of the mimic muscles. The patient was able to perform voluntary contractions of the left corrugator glabellae muscle and of the left corner of the orbicular oral muscle; these contractions were recorded electromyographically. The stimulation of the right facial nerve elicited responses in the referred left mimic muscles. This circumstance indicated their activity to be due to contralateral reinnervation by the intact facial nerve. The blink reflex examination evoked no response on the left side, while the blinik reflex on the right side was elicited with both its components, both upon ipsi- and contralateral stimulation.     

Silent period in the mentalis muscle induced by facial nerve and cutaneous stimulation.

The aim of this study was to demonstrate that silent periods of the mentalis muscle are induced after facial nerve stimulation and cutaneous stimulation in normal subjects. When the marginal mandibular branch of the facial nerve and the cutaneous nerve in areas adjacent to the lower lip were stimulated during slight voluntary contraction of the mentalis muscle, silent periods were elicited with surface electrodes on the mentalis muscle. The early phase and the late phase of the silent period were elicited by marginal mandibular branch stimulation. The early phase of the silent period was recognized following the F waves and it disappeared at 36.3 msec. The average duration of the late phase of the silent period was 59.2 msec, with an average latency of 62.5 msec. Only the late phase of the silent period after cutaneous stimulation could be elicited, with a duration and latency of 55.9 msec and 54.0 msec respectively. The authors conclude that the silent period is able to be elicited in the mentalis muscle by peripheral nerve stimulation, and is one of the late responses in facial muscles.     

F-waves and facilitated late responses of the mentalis muscle in patients with a cerebrovascular accident

F-waves in the extremities result from the backfiring of antidromically activated anterior horn cells and F-waves of the mentalis muscle can be also elicited after stimulation of the marginal mandibular branch of the facial nerve. In order to investigate the influence of the descending pathway of the excitability of the facial motonucleus, the F-wave of the mentalis muscle and the facilitated late response, which follows F-waves and which seems to be the snout reflex due to their similar latency and habituation, were studied in 11 conscious patients with a hemispheric cerebrovascular accident (CVA) presenting with hemiparesis, and in 10 unconscious patients with CVA or head injury. The duration and the persistence of the F-waves increased significantly statistically on the normal side in the CVA patients compared with those of the palsy side and the normal subjects. In comatose patients the F-waves and the facilitated late response were not elicited. The latency (46.1 +/- 13.3 msec) of the facilitated late responses in the unconscious patients tended to increase compared with the latency (36.6 +/- 4.3 msec) in the conscious patients. These findings suggest that the hyperexcitability of the facial motoneuron is ipsilateral to any hemispheric lesion; the hemispheric lesion exerts a bilateral excitatory influence on the interneuron of the facilitated late response: and that the reticular formation may influence the facial motoneuron and any interneurons concerned in the facilitated late response. F-waves and facilitated late responses should be further examined as neurophysiologically useful diagnostic methods.     

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.     

Blink reflex recovery in facial weakness: an electrophysiologic study of adaptive changes

OBJECTIVE: To study the electrophysiologic effects of unilateral facial weakness on the excitability of the neuronal circuitry underlying blink reflex, and to localize the site of changes in blink reflex excitability that occur after facial weakness. BACKGROUND: Eyelid kinematic studies suggest that adaptive modification of the blink reflex occurs after facial weakness. Such adaptations generally optimize eye closure. A report of blepharospasm following Bell's palsy suggests that dysfunctional adaptive changes can also occur. METHODS: Blink reflex recovery was evaluated with paired stimulation of the supraorbital nerve at different interstimulus intervals. Comparisons were made between normal control subjects and patients with Bell's palsy who either recovered facial strength or who had persistent weakness. RESULTS: Blink reflex recovery was enhanced in patients with residual weakness but not in patients who recovered facial strength. Facial muscles on weak and unaffected sides showed enhancement. In patients with residual weakness, earlier blink reflex recovery occurred when stimulating the supraorbital nerve on the weak side. Sensory thresholds were symmetric. CONCLUSION: Enhancement of blink reflex recovery is dependent on ongoing facial weakness. Faster recovery when stimulating the supraorbital nerve on the paretic side suggests that sensitization may be lateralized, and suggests a role for abnormal afferent input in maintaining sensitization. Interneurons in the blink reflex pathway are the best candidates for the locus of this plasticity.     

Orbicularis oculi and orbicularis oris reflexes in blepharospasm and torticollis spasmodica during spasm-free intervals

To investigate possible abnormalities of the blink reflex pathways, we analyzed the latencies and amplitudes of the blink reflex responses in the orbicularis oculi (Ooculi) muscle, following supraorbital nerve stimulation, in 19 patients with blepharospasm, 16 patients with torticollis spasmodica and 22 control subjects. Furthermore, in order to examine the suprasegmental control of the responses, the reflex responses were also evoked in the orbicularis oris (Ooris) muscle after stimulation of the ipsilateral supraorbital nerve. The responses were recorded only when subjects had no contractions of the eyelid muscles, either involuntarily, voluntarily or spontaneously; this could be controlled by a sound signal. The metrics of the reflex responses in the Ooculi and Ooris muscles in patient groups were comparable to those in controls. Our data indicate that the afferent and efferent pathways of the reflex arc and the suprasegmental control of the reflex are intact in patients with blepharospasm and torticollis spasmodica, at least during spasm-free intervals. Alterations of responses may occur during spasms due to either segmental or suprasegmental changes.     

Electrophysiological evidence for crossed oligosynaptic trigemino-facial connections in normal man.

A crossed short latency component (R1) of the human blink reflex could be elicited in orbicularis oculi muscles to stimulation of the contralateral supraorbital nerve, when infraliminal conditioning stimuli were applied to various cutaneous afferents of the body (facial, upper and lower limbs). The crossed R1 responses appeared when the time interval between the conditioning and the test stimuli was of 30 to 40 ms, 50 to 65 ms and 95 to 110 ms for facial, upper and lower limbs afferents respectively. For the same time intervals, these conditioning volleys also exerted a facilitatory effect on the ipsilateral R1 responses. Furthermore, crossed R1 responses were also obtained during supraspinal facilitation induced by a voluntary contraction of the eyelids. These data show that crossed oligosynaptic trigemino-facial reflex connections exist in normal subjects, which become functional when adequate conditioning stimuli are available.