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.     

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.     

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.     

Primary hemifacial spasm: a neurophysiological study.

A series of 53 cases of primary hemifacial spasm have been evaluated by means of blink reflexes and their results compared with a normal control group. Reflex responses were obtained by percutaneous electrical stimulus of both the supraorbital nerve (trigemino-facial reflex), and the facial nerve at the stylo-mastoid region (facio-facial reflex). The R2 response was considered abnormal when its latency was shortened (hyperactivity) or delayed (hypoactivity). Thirty-six out of 53 cases with primary hemifacial spasm showed abnormal responses, with a combination of facial nerve impairment (delayed R2 in the facio-facial reflex) and trigeminal-facial hyperactivity (shortened R2 in the trigemino-facial reflex). Five cases showed hyperactivity in both the trigemino-facial reflex and the facio-facial reflex reflexes. These results suggest a state of hyperexcitability, probably at the level of the facial nucleus, combined with a peripheral facial nerve involvement in a high proportion of patients with primary hemifacial spasm.     

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.     

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.     

F-responses of human facial muscles. A single motoneurone study

Late responses to percutaneous electrical stimulation of the facial nerve of normal man were studied in single facial motoneurones by means of single fibre EMG recordings. On the basis of latency variation and the relationship to direct responses, late responses could be differentiated in 4 types: reflex responses with small and large latency variation respectively; axon reflexes due to branching of the motor axons, and recurrent responses following antidromic activation of the motor axons.The reflex responses were due to stimulation of neighbouring trigeminal afferents and corresponded to the first and second component of the blink reflex. Axon reflexes indicate that branching of the axons may occur even in the intracranial and perhaps in the intracerebral course of the nerve. Recurrent responses exhibited very small variations in latency; they could be facilitated by subthreshold depolarization of the soma-dendritic membrane.     

Corneal reflex in normal and pathological subjects

The orbicularis oculi response can be evoked both by mechanical stimulation of the cornea (corneal reflex) and by electrical stimulation of the skin overlying the supraorbital nerve (blink reflex). Mechanical stimuli to the cornea activate A delta and C free nerve endings of the corneal mucosa. Electrical stimuli to the supraorbital nerve activate A beta, A delta and C fibers of the nerve trunk. Both reflexes present a bilateral late response, but the blink reflex shows in addition an early ipsilateral component (R1), which has never been observed with the corneal stimulation in man. We have developed a simple technique of electrical stimulation of the cornea which provides stable responses and allows precise measurements of threshold and latency of the reflex. In normal subjects, the threshold ranged from 50 to 350 microA, and the maximal stimulus that the subject could bear (tolerance level) ranged from 1000 to 2500 microA. The minimal latency to tolerance level stimuli was 39 +/- 3 msec. The latency difference between the direct responses evoked from the two opposite corneas never exceeded 8 msec and the difference between the direct and consensual responses elicited from the same cornea never exceeded 5 msec. An early ipsilateral component similar to the R1 response of the blink reflex was not observed, even with supramaximal stimulation. The electrically evoked corneal reflex was normal in 10 cases of essential trigeminal neuralgia, while the responses showed significant abnormalities in 18 subjects submitted to thermocoagulation of the Gasserian ganglion as a treatment of neuralgic pain, as well as in 2 cases of symptomatic neuralgia.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

The n10 component of the ocular vestibular-evoked myogenic potential (oVEMP) is distinct from the R1 component of the blink reflex

ObjectiveBone-conducted vibration (BCV) in the midline at the hairline (Fz), results in short latency potentials recorded by surface electrodes beneath the eyes – the ocular vestibular-evoked myogenic potential (oVEMP). The early negative component of the oVEMP, n10, is due to vestibular stimulation, however it is similar to the early R1 component of the blink reflex. Here we seek to dissociate n10 from R1.MethodsSurface potentials were recorded from the infraorbital electromyogram of 10 healthy subjects, 6 patients with bilateral vestibular loss, 2 with unilateral vestibular loss, 4 with facial palsy and 3 with facial and vestibular nerve lesions on the same side. BCV was delivered at Fz, the inion, the glabella or the supraorbital ridge using a tendon hammer or a bone-conduction vibrator.ResultsOnset latencies of the n10 evoked by taps at Fz or inion were significantly shorter than the R1 components of blink responses to supraorbital and glabellar stimuli. Upward gaze increased the amplitude of n10 but not R1. The n10 was absent bilaterally in patients with bilateral vestibular loss and beneath the contralesional eye in patients with unilateral vestibular loss, but in both these groups of patients R1 was preserved. In severe facial palsy the R1 component was absent or delayed and attenuated ipsilesionally, but n10 was preserved bilaterally. In subjects with unilateral facial and vestibular nerve lesions (Herpes Zoster of the facial and vestibulocochlear nerves) the dissociation was complete – the ipsilesional R1 was absent or attenuated whereas the ipsilesional n10 was preserved.Conclusionsn10 is distinguished from R1 by its earlier onset, laterality, modulation by gaze position and dissociation in patient groups.SignificanceThe n10 component evoked by BCV at Fz is not the R1 component of the blink reflex.     

The corneal reflex and the R2 component of the blink reflex

A reflex contraction of the human orbicularis oculi muscles can be evoked by stimulation of either the supraorbital region ("blink reflex") or the cornea ("corneal reflex"). We found that the latency of the corneal reflex was longer, and the duration was longer than the R2 component of the blink reflex. The absolute refractory period of the R2 component of the blink reflex was longer after supraorbital than after corneal conditioning stimulation. When the R2 component of the blink reflex was habituated by repetitive stimuli, stimulation of the cornea still evoked a reflex, but supraorbital stimulation produced only a depressed R2 response. These findings suggest that the two reflexes do not have identical neural connections.     

Related timing for peripheral and central plasticity in hypoglossal-facial nerve anastomosis

The aim of this work was to determine the role of peripheral facial muscle reinnervation in the central reorganization of the blink reflex (BR) after hypoglossal-facial anastomosis (HFA). An electrophysiological study was performed on seven patients who underwent HFA after facial nerve transection during surgery for acoustic neuroma. HFA was performed within 15 days after surgery in five patients (group 1) and later for the two others (group 2). We studied the motor responses (MR) and the BR evoked on the affected side, before and over 3 years after the HFA. The MR appeared by the third month for the first group, and by the sixth and twelfth for the second group. After 36 months, the amplitude of MR was significantly higher than its control value, showing hyperinnervation of the facial muscles. Study of the BR evoked only an R1-type blink response that was observed 4 and 6 months after the MR for groups 1 and 2, respectively. This central reorganization appeared closely correlated with muscle reinnervation and its related timing. The occurrence of peripheral nerve-muscle contacts seems to be a necessary condition for reorganization of the trigemino-hypoglossal-facial reflex.     

Mandibular nerve involvement in diabetic polyneuropathy and chronic inflammatory demyelinating polyneuropathy

Sensory complaints in the area of the mandible and mouth often escape notice or remain undiagnosed. Using electromyographic recording of the trigeminal reflexes and motor responses, we sought trigeminal dysfunction in 50 patients with peripheral neuropathy, and tried to gain pathophysiological information on the mechanisms provoking trigeminal damage. Trigeminal reflex recordings (early and late blink reflex after supraorbital stimulation, early and late masseter inhibitory reflex after mental stimulation, and jaw jerk) disclosed abnormalities caused by sensory trigeminal neuropathy in 8 out of 15 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 13 out of 23 patients with severe diabetic polyneuropathy, and in none of 12 patients with mild diabetic polyneuropathy. Six patients had abnormal motor responses in facial or masseter muscles. The response affected most frequently was the masseter early inhibitory reflex (also called first silent period, SP1) after mental nerve stimulation, its latency being strongly delayed. We found these long delays not only in patients with CIDP, but also in diabetic patients with severe polyneuropathy. We conclude that peripheral polyneuropathies often cause subclinical damage to the trigeminal nerve, especially to its mandibular branch. We believe that the nerve fibers running along the alveolar–mandibular pathway are more exposed to damage because of their cramped anatomical route in the mandibular canal and below the internal pterygoid muscle and fascia. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1673–1679, 1998     

Hypoglossal-facial nerve anastomosis: a clinical and electrophysiological follow-up.

Eight patients with acoustic neuroma and five patients with hemifacial spasm, who had undergone hypoglossal-facial nerve anastomosis 1-14 years previously, were reviewed clinically and electrophysiologically with an electrically elicited blink reflex. Functional recovery from the anastomosis, as rigorously judged on a scale of good, fair and poor, was fair to poor. Electrically it was found that the blink reflex was present in eight patients, suggesting facial nerve re-innervation of the facial musculature. This was confirmed by the mild recurrence of hemifacial spasm in four patients. Implications for the future role of this operative procedure are discussed.     

Blink reflex abnormalities in children with Tourette syndrome

Tourette syndrome (TS) is a common disorder which typically occurs during childhood or early adolescence. There is no definitive diagnostic test for TS. The objective of this study was to demonstrate whether neurophysiological abnormalities of the blink reflex can be observed in children with TS. We enrolled 15 children with TS, diagnosed according to DSM IV Diagnostic Criteria, and 15 controls. The blink reflex was elicited by stimulating the supraorbital nerve in order to measure the early response (R1), homolateral and contralateral R2 (late) responses, amplitude of R1 and duration of R2. The mean duration of R2 was significantly longer in TS patients than in the controls ( P  < 0.001, Student's t -test). An abnormal pattern of the blink reflex can be, even in childhood, an early neurophysiologic marker of TS, which is not related to the duration of TS or to the age of onset.     

Features of the blink reflex in individuals at risk for Huntington's disease.

The aim of the study was to correlate the features of the blink reflex (BR) with the genetic abnormalities and the clinical findings in patients with Huntington's disease (HD) and asymptomatic gene carriers. Twenty patients with HD and 20 relatives were studied. Mutation analysis was performed for the CAG expansion within the HD gene using HD 333-HD 447 as oligonucleotide primers. The BR was elicited transcutaneously by electrical stimulation of the right supraorbital nerve. The recovery curve of the R2 and R3 responses after a conditioning stimulus was evaluated. R2 latency and duration and R3 duration were significantly increased in HD patients and in presymptomatic carriers in comparison with controls; reduced R2 recovery was also clear in both HD and gene-carrier relatives. In HD patients, the R2 latency increase correlated significantly with the severity of facial chorea. The R2 abnormalities are probably caused by impaired suprasegmental control by the basal ganglia over brainstem interneurons, which may precede the onset of involuntary movements, probably conditioning the severity of facial chorea during development of the disease.     

Orbicularis oculi responses to stimulation of nerve afferents from upper and lower limbs in normal humans

A brief mechanical or electrical stimulus to peripheral nerve afferents from the upper and lower limbs elicited a small and inconsistent EMG response of the orbicularis oculi muscles. This response was facilitated when the stimuli were delivered at fixed leading time intervals, of 45–300 ms, with respect to a supraorbital nerve electrical stimulus. Also, the peripheral nerve stimulus modified the conventional blink reflex responses, inducing facilitation of R1 and inhibition of R2. These results suggest a complex processing of sensory inputs from the face and the limbs at the brainstem, where they are probably integrated in a network of interneurons influencing the excitability of facial motoneurons.     

Cranial nerve conduction and needle electromyography in patients with acoustic neuromas: A model of compression neuropathy

Of 45 patients with acoustic neuromas (0.3–5.0 cm), 73% had facial nerve impairment on electrophysiologic testing, but only 16% had facial weakness. Cranial nerve conduction was the most sensitive measurement, especially prolongation of the ipsilateral R1 latency of the blink reflex compared with that of the contralateral reflex. The severity of nerve conduction abnormality was highly correlated with tumor size. Our results confirm and quantitate the sensitivity of nerve action potential latency in response to chronic nerve compression. © 1994 John Wiley & Sons, Inc.     

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.     

Long‐term depression‐like plasticity of the blink reflex for the treatment of blepharospasm

Our previous work showed a beneficial therapeutic effect on blepharospasm using slow repetitive transcranial magnetic stimulation, which produces a long‐term depression (LTD)‐like effect. High‐frequency supraorbital electrical stimulation, asynchronous with the R2 component of the blink reflex, can also induce LTD‐like effects on the blink reflex circuit in healthy subjects. Patients with blepharospasm have reduced inhibition of their blink recovery curves; therefore, a LTD‐like intervention might normalize the blink reflex recovery (BRR) and have a favorable therapeutic effect. This is a randomized, sham‐controlled, observer‐blinded prospective study. In 14 blepharospasm patients, we evaluated the effects of high‐frequency supraorbital stimulation on three separate treatment days. We applied 28 trains of nine stimuli, 400 Hz, either before or after the R2 or used sham stimulation. The primary outcome was the blink rate, number of spasms rated by a blinded physician and patient rating before, immediately after and 1 hour after stimulation while resting, reading, and talking; secondary outcome was the BRR. Stimulation “before” and “after” the R2 both showed a similar improvement as sham stimulation in physician rating, but patients felt significantly better with the before condition. Improvement in recovery of the blink reflex was noted only in the before condition. Clinical symptoms differed in the three baseline conditions (resting, reading, and talking). Stimulation before R2 increased inhibition in trigeminal blink reflex circuits in blepharospasm toward normal values and produced subjective, but not objective, improvement. Inhibition of the blink reflex pathway by itself appeared to be insufficient for a useful therapeutic effect. © 2013 Movement Disorder Society