R1 Latency Research Articles

Blink reflex discloses CNS dysfunction in neurologically asymptomatic patients with systemic sclerosis

Objective: To investigate trigeminal-nerve, brain-stem, and brain function, in order to disclose a possible nervous system involvement in neurologically asymptomatic systemic sclerosis (SSc) patients. Methods: Using a standard electromyographic (EMG) technique, we recorded the early (R1) and late (R2) components of the blink reflex in 35 SSc patients with no history or signs of cranial-nerve impairment and 20 control subjects. SSc patients were classified as limited or diffuse SSc and also evaluated for disease duration, autoantibody pattern (ANA, ACA, Scl70) and skin score (by Rodnan modified method). Results: Whereas no SSc patients had an abnormal R1, six (18%) had delayed R2 responses. We found no correlation between R2 latency and clinical or laboratory data. Conclusions: Whereas previous studies reported both R1 and R2 abnormalities (reasonably due to trigeminal neuropathy) in symptomatic SSc patients, we found selective abnormalities of the R2 components in asymptomatic patients. The selective R2 abnormality is secondary to a central dysfunction, either because of a direct impairment of the polysynaptic circuits in the medulla, or because of a decreased cortico-reticular drive on these circuits. The lack of overt trigeminal symptoms in our patients favours a suprasegmental dysfunction, possibly due to microvascular lesions disseminated in the subcortical white matter.

Brainstem evaluation in children with primary nocturnal enuresis.

We investigated the brainstem integrity in children with primary nocturnal enuresis (PNE) using auditory brainstem responses (ABR), blink reflex and exteroceptive suppression of the masseter muscle. We examined 23 children with PNE (16 male, 7 female; mean age: 10.4 years) and 19 control subjects (11 male, 8 female; mean age: 11.8 years). ABR parameters such as wave latencies, amplitudes and interpeak latencies and blink reflex parameters such as R1 and R2 amplitude and latencies were not significantly different between the 2 groups. Although S2 parameters of the exteroceptive suppression of the masseter muscle were easily and completely obtained from the control subjects, in the PNE group S2 onset latency and duration were not recorded in 26% of the study children (n = 6) (P = 0.01). S2 duration time was significantly lowered in the enuretic group (left side: P = 0.001 and right side: P = 0.003). S2 duration time changes in the enuretic group supports a possible brainstem dysfunction in children with PNE.

Using the Blink Reflex as Measured by Electromyogram to Assess Cranial Nerve Involvement in People Affected by Leprosy

Damage to the peripheral nervous system is particularly frequent in leprosy patients. Trigeminal and facial nerves are among the most commonly affected. The aim of our study was to evaluate the efficacy of the blink reflex as a method for diagnosis of cranial nerve involvement in people affected by leprosy. We studied 37 affected people (mean age: 38 yrs, 20 female and 17 male) and 35 age-matched healthy subjects (mean age: 34 yrs, 20 female and 15 male). Blink reflexes were obtained after unilateral electrical stimulation of the supraorbital nerve for quantitative analysis of 3 responses, early ipsilateral phasic component (R1), late ipsilateral tonic component (R2i), and late contralateral tonic component (R2c). Nerve conduction parameters were studied in all subjects. The latencies of both the ipsilateral early phasic component (R1) and bilateral late tonic components (R2i and R2c) in people affected by leprosy were significantly prolonged compared with the controls. Out of 37 people affected by leprosy, 22 (59%) showed abnormalities R1 latency, 28 (75%) R2i latency and 31 (83%) R2c latency. No correlation was observed between prolonged latencies and duration of the disease. We conclude that blink reflex testing, which can be easily and rapidly performed in an EMG laboratory using standard equipment, can provide useful and objective information for the diagnosis of cranial nerve lesions and for the determination of the degree thereof.

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

Neurology. 2002;58:1234‐1238.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. Comment: This abstract from Dr. Chris Diener's group reports large changes in the AUC for onset latencies between headache affected and nonaffected sides. Drug treatment effects were small. No statistical comparisons were reported. This noninvasive technique may be useful in further exploring the mechanisms which underlie the temporary sensitization of central trigeminal neurons during acute migraine attacks. DSM

Blink reflex: comparison of latency measurements in different human races

The blink reflex latencies and cephalometric indexes were analysed in 30 male volunteers from three different races, 10 white, 10 black, and 10 Oriental. Ages ranged from 15 to 59 years, height from 1,60 to 1,80 m, and weight from 60 to 80 kg. Blink reflexes were obtained after unilateral electric stimulation of the supraorbital nerve for quantitative analysis of 3 responses, early ipsilateral (R1), late ipsilateral (R2i) and late contralateral (R2c), obtained from the orbicularis oculi muscle. Cephalometric indexes were calculated by multiplying the ratio between the longer transverse and the longer sagital head diameters by 100. The R1, R2i and R2c latencies were consistent with other published papers revealing no differences between the different racial groups. The mean of the cephalometric indexes of each group were consistent with respective racial characteristics. This study revealed that there are no differences between R1, R2i and R2c latencies in the 3 different studied races.

Objective evaluation of infraorbital nerve involvement in maxillary lesions by means of the blink reflex.

To objectively evaluate the effects of maxillary lesions on the infraorbital nerve (ION). We investigated the latencies (R1, R2) of the blink reflex, stimulating the infraorbital foramen electrically (18 mA, 0.2 millisecond). Twenty-two patients with unilateral maxillary lesions were enrolled. Ten patients showed delayed or absent R1 on the lesion side. Four of 20 patients showed delayed difference in R2 latency. Ten (77%) of 13 patients with lesions along the ION pathway showed an abnormal blink reflex. Only 3 patients demonstrated a normal blink reflex despite a lesion along the pathway of the ION. All patients whose ION pathway was intact showed a normal blink reflex. These results suggested that lesions along the ION pathway may impair the afferent pathway of the blink reflex. The blink reflex may be valuable to evaluate maxillary lesions objectively. Furthermore, R1 is more effective than R2 in detecting ION defects.

Pathophysiology of facial nerve paralysis induced by herpes simplex virus type 1 infection.

Herpes simplex virus type 1 (HSV-1) has been proven to be a cause of Bell's palsy; however, the underlying pathophysiology of the facial nerve paralysis is not fully understood. We established a mouse model with facial nerve paralysis induced by HSV-1 infection simulating Bell's palsy and investigated the pathophysiology of the facial nerve paralysis. The time course of the R1 latency in the blink reflex tests paralleled the recovery of the facial nerve paralysis well, whereas electroneurographic recovery tended to be delayed, compared to that of the paralysis; these responses are usually seen in Bell's palsy. On histopathologic analysis, intact, demyelinated, and degenerated nerves were intermingled in the facial nerve in the model. The similarity of the time course of facial nerve paralysis and the electrophysiological results in Bell's palsy and the model strongly suggest that the pathophysiological basis of Bell's palsy is a mixed lesion of various nerve injuries.

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.

Brain-stem compression in vertebrobasilar dolichoectasia. A multimodal electrophysiological study

Objective: To evaluate the effects of mechanical compression of the brain-stem in patients with vertebrobasilar dolichoectasia (VBD). Methods: In the framework of a prospective, observational study that collected clinical and laboratory data in patients with VBD, we studied 20 patients with compression of the brain-stem due to ectatic, tortuous basilar or vertebral arteries. Patients with cerebral lesions other than small lacunae in the white matter of the cerebral hemispheres were excluded from the study. Patients underwent vestibular and auditory function testing, including brain-stem auditory evoked potentials (BAEPs), blink reflex (BR), somatosensory evoked potentials (SEPs), and motor evoked potentials (MEPs). Results: Almost all of the patients complained of auditory or vestibular symptoms and none had symptoms or signs of impairment of long tracts or the facial and trigeminal nerves. The most consistent findings were BR abnormalities with prolongation of ipsilateral R1 latency in cases of compression of the pons (10/16) and prolongation of the R2 and R2c latencies with compression of the medulla oblongata (5/15). Subclinical impairment of corticospinal pathways was found in 13 out of 25 instances of compression, and this was more frequent with compression of the pons. Abnormal BAEPs or SEPs were less frequently encountered, and only in cases with compression of the pons. Conclusions: Neurovascular compression of the brain-stem, even with severe distortion, is seldom associated with overt clinical signs, whereas subclinical dysfunctions are relatively frequent. The central pathways of the BR and the corticospinal pathways are more susceptible to compression than acoustic and sensory pathways. BR, MEP and BAEP data provide a functional evaluation of the brain-stem and some cranial nerves, which is lacking in imaging studies. Functional investigations may be useful in the long-term management of these patients, since VBD may be progressive and surgical correction may be required at some stage.

Wavelet decomposition of the blink reflex R2 component enables improved discrimination of multiple sclerosis

Objectives: The blink reflex R2 component was subjected to wavelet decomposition for time feature extraction in order to classify the functional status of patients with multiple sclerosis.Methods: The blink reflex was recorded bilaterally with unilateral stimulation of the supra-orbital nerve in 37 normal subjects and 9 patients with multiple sclerosis (MS). The late component, R2, was subjected to time-frequency decomposition using the Daubechies-4 wavelet. Using the time-frequency coefficients, the mean time of the R2 wave as well as the standard deviation of the R2 interval were calculated in each trial. The wavelet transform enables noise reduction by allowing selective use of frequency bands with high signal-to-noise ratio for time feature extraction; therefore automatic estimation of time parameters is robust. The distribution densities of the mean and the standard deviation of the R2 wave duration for the set of trials for each subject were computed.Results: An appreciable difference in the densities of the two parameters extracted in the wavelet domain was seen between normals and patients. This is in contrast to the onset latency of R2 which poorly discriminates MS patients from normals.Conclusion: The results suggest that the mean and standard deviation of the R2-time robustly estimated using wavelet decomposition can be used to support clinical diagnosis in tracking the functional status of patients with diseases like multiple sclerosis.

Blink Reflexes and Lateral Spreading in Patients with Synkinesia after Bell’s Palsy and in Hemifacial Spasm

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

Cremasteric reflexes of boys with descended, retractile, or undescended testes: An electrophysiological evaluation

Background/Purpose: Retractile testis traditionally has been regarded as suprascrotal location of testis resulting from hyperactivity of the cremasteric reflex (CR). However, the activity of CR is evaluated poorly in the literature. Electrophysiological characteristics of CR in boys with various testicular localizations have been evaluated comparatively. Methods: Cremasteric responses that were evoked by electrical stimulation of the upper-inner aspect of thigh were recorded using a concentric needle electromyography (EMG) electrode inserted into the cremaster muscle. Evoked EMGs of groups, each consisting of 10 boys with bilateral descended (DT), unilateral retractile (RT), or unilateral underscended testes (UT) were compared for response latencies and durations. Results: Three components with different onset latencies (R1, R2, and R3) were identified in EMG responses. In patients with UT, the latency of the R1 was shorter than that of the patients with DT, and the duration of R2 was longer than those of the patients with DT and RT. The differences between patients with RT and DT regarding the latency and duration of R1 and R2, although similar to those differences between UT and DT, were not significant. There were no significant differences of the latencies of R3 between groups. In patients with RT and UT, response latency and duration in the descended and retractile-undescended sides were similar. Conclusions: Defined by shortened latency and prolonged activity of cremasteric responses, which probably reflect a diminished neuronal inhibitory control, CR is hyperactive in UT. Dysinhibited motor neurons leading to overactivity of cremaster muscle might have hampered the descent of testis. Our results do not provide a definite support for or against the hypothesis of CR hyperactivity in RT.

Blink Reflex in Migraine and Tension‐Type Headache

The blink reflex was studied in 19 patients with migraine, 10 patients with tension-type headache, and 30 healthy controls. Significantly lower values of R2 and R2' amplitude and size were found in the migraine group, compared with the healthy control group. The differences were independent of the stimulation side (headache or nonheadache) and highly significant (P<0.001). The abnormalities of R2 and R2' amplitude and size were found only during the headache phase of migraine, being normal between migraine attacks. R1 latency and amplitude were normal in all patients. The blink reflex was normal in all the patients with tension-type headache. Subcutaneous injection of sumatriptan in 10 of the 19 migraineurs, during the headache phase, restored R2 and R2' amplitude and size values to normal. Our findings indicate that the brain stem interneuron part of the blink reflex arc may be diffusely suppressed in migraine, only during the headache phase. Furthermore, blink reflex may be an objective laboratory method to monitor the effectiveness of specific drugs proposed for the treatment of migraine.

Voluntary eyelid contraction modifies the blink reflex recovery cycle.

In order to determine the extent to which the recovery cycle of the blink reflex is modified by voluntary contraction of the eyelids we investigated the electrically elicited blink reflex with paired stimuli of identical intensity in 9 healthy subjects. We pseudorandomly administered two interstimulus intervals (150 ms and 250 ms) in three different conditions of voluntary contraction of the orbicularis oculi muscle (relaxed, mild lid closure and strong lid closure). Our results show that inhibition of the R2 response following the second stimulus is significantly reduced with voluntary contraction. In addition, we found significantly larger amplitudes and shorter latencies of R1 and R2 with voluntary contraction. We conclude that in healthy subjects, voluntary eyelid contraction causes facilitation or disinhibition not only in the nuclei of the seventh cranial nerve, but also in the polysynaptic pathway of the R2. The possible implications on the interpretation of clinical data are discussed.

ウイルス性顔面神経麻ひの病態に関する研究 電気生理学的および病理組織学的検討

Bell's palsy is the most common cause of peripheral facial nerve paralysis. Although herpes simplex virus type 1 (HSV-1) infection has been strongly suggested as a cause of Bell's palsy, the pathomechanism of the facial nerve paralysis is unclear. Previously, we had succeeded in producing an animal model of acute, transient and homolateral facial paralysis by inoculating HSV-1 into the auricle, simulating Bell's palsy. To clarify the mechanism of this facial nerve paralysis, electrophysiological testing of the trigemino-facial reflex (blink reflex) and electroneuronography (ENoG) were carried out, and a histopathological study of the facial nerve was subsequently performed. The blink reflex and ENoG were examined twice ; during facial paralysis on day 10 and after recovery on day 17. The R1 latency of the blink reflex was prolonged or disappeared on the paralyzed side during facial paralysis, but recovered in all animals with the corresponding recovery of facial nerve paralysis. ENoG values were inconsistent during facial nerve paralysis and did not normalize even after complete recovery of the facial nerve paralysis. The histopathological studies demonstrated that mixed nerve damage, demyelination and axonotomesis, were present, although demyelination was dominant. Collectively, the electrophysiological and histopathological findings suggested that the pathomechanism of facial nerve paralysis caused by HSV-1 infection is mainly due to demyelination of the nerve, which was represented as a conduction block in electrophysiological testing. The present study suggested that the facial nerve damage underlying Bell's palsy involves mixed nerve damage including demyelination and axonotomesis, and the prognosis of facial nerve paralysis is dependent on the balance of these two kinds of nerve damage.

Peroxisomal bifunctional enzyme deficiency: serial neurophysiological examinations of a case

We report on a case of 21-month-old girl with peroxisomal bifunctional enzyme deficiency, which was diagnosed by means of complementation analysis. Serial neurophysiological examinations were also carried out. The motor and sensory nerve conduction velocities of the median nerve showed lower borderline values at 3 months of age and were within normal range at 11 months of age. Later, those velocities had gradually decreased. The electrically elicited blink reflex at 3 months of age showed the prolongation of latencies of R1, R2 and R2′ and the interpeak latencies of R1, R2 and R1 -R2′. Furthermore, RI, R2 and R2′ showed prolonged latencies at 11 months of age and were absent at 15 months of age. The auditory brainstem response (ABR) showed, bilaterally, normal latency of wave I, prolonged interpeak latencies of waves I–V. At 11 months of age, waves III and IV–V of ABR were detected, but their amplitude was very low. At the age of 15 months ABR was absent. These results and the following report are valuable for understanding the pathogenesis of neurological symptoms.

Inhibition of the blink reflex R2 component after supraorbital and index finger stimulations is reduced in cluster headache: an indication for both segmental and suprasegmental dysfunction?

Peripheral as well as central mechanisms are thought to play a role in cluster headache pathogenesis. We have studied recovery curves of the R2 component of the blink reflex after conditioning by supraorbital or index finger stimuli in 10 episodic cluster headache (CH) patients during a cluster period and in 10 healthy controls. There was no significant change of R2 threshold, latency or area in CH patients. After paired supraorbital stimuli, R2 recovered more rapidly in patients on the symptomatic side. After index stimulations, R2 recovery was more rapid on both symptomatic and non-symptomatic sides in patients compared to controls. Naloxone (0.4 mg) i.v. in two subjects partially reversed the R2 suppression induced by index finger stimuli. The unilateral decrease of R2 inhibition after a segmental supraorbital stimulus most likely reflects sensitisation in the spinal trigeminal nucleus. Whether the latter is due to irritation of the ophthalmic nerve within the cavernous sinus region, which is thought to be pivotal in CH pathogenesis, remains to be proven. In addition, we propose that the bilateral deficit of R2 inhibition after an extrasegmental exteroceptive stimulus might reflect hypoactivity of reticular nuclei, possibly because of reduced central opioid activity.

Temporal integration shown in the late component of the human blink reflex

The effect of closely spaced stimulus pairs (S1–S2), one at or above threshold for eliciting the second electromyographic burst of the cutaneous blink reflex (R2) and one below threshold intensity, on the latency, duration, and area of R2 was examined in four experiments. The size of the R2 elicited by a threshold S1 (but not by an S1 at three times threshold intensity) was augmented by threshold or near-threshold S2s that appeared after stimulus onset asynchronies of 4, 8, and 16 msec. More intense S2s had a greater effect on R2 size and led also to a slight shortening of R2 latency. Although R2 augmentation was accompanied by a modest increase in response duration, this increase in duration was by itself insufficient to account for the augmentation of response amplitude. Subreflexogenic S1s (at 0.1, 0.2, 0.4, and 0.8 times R2 threshold intensity) did not affect the R2 elicited by an S2 at threshold intensity or two times threshold intensity. Unlike the simple brainstem pathway which mediates R1, the more complex brainstem pathway which mediates R2 is capable of summing stimulus energy over time.

Conditioned Enhancement of the Early Component of the Rat Eyeblink Reflex

Conditioned enhancement of the rat eyeblink reflex was studied using as a response measure the electromyogram (EMG) in the orbicularis oculi (oo) muscle, which is responsible for the active force generating eyelid closure. During a reflex eyeblink, the EMG evidences both a short-latency (R1) and a long-latency (R2) component, mediated by different circuits. The R2 response exhibits several experience- or use-dependent modifications. We were interested in the modifiability of the neurophysiologically simpler R1 response. Experiments were designed to determine whether the R1 response can be enhanced by a conditioned stimulus (CS) that has been explicitly paired with an aversive unconditioned stimulus (US). The R1 response was elicited by electrical stimulation of the supraorbital branch of the trigeminal nerve. Following long-delay conditioning, the CS produced a significant R1 enhancement and latency decrease that were dependent upon explicit CS–US pairings. The CS by itself produced no significant EMG response, consistent with a modulatory rather than additive effect. This is the first demonstration that the R1 response can be associatively modulated. Based on other evidence, we hypothesize that the CS-produced enhancement results from a relatively direct projection from the amygdala to the R1 circuit. As an index of aversive conditioning, R1 enhancement may prove to be a useful expression system because it offers high temporal resolution and the underlying circuitry is relatively simple—the shortest path from the fifth nerve to the muscle consisting of only two central synapses.

Blink reflex in cerebral palsy: evaluation of late components in patients with normal auditory brainstem responses.

The electrically elicited blink reflex was examined and evaluated quantitatively in 60 controls and seven patients with cerebral palsy due to perinatal asphyxia who exhibited normal auditory brainstem responses. In the controls, the early component (R1) latency changed slightly from infancy to adulthood, and the late component (R2 and R2') latencies decreased to adult values by 4 to 6 years of age. The electromyographic activity of R2 and R2' increased later and became mature in the young adolescent period. Prolonged R2 latency and decreased R2 amplitude were observed more frequently than R1 abnormalities in the patients. The electromyographic activity of R2 in the patients was lower than that in control subjects more than 13 years old. Almost all patients showed bilateral cerebral atrophy and dilated lateral ventricles, but only one patient exhibited distinct pontine atrophy on cranial computed tomographic scan. These electrophysiologic abnormalities suggest that decreased excitability of interneurons of the reflex arc was present in the patients, particularly in older ones. The blink reflex test seems to be more sensitive than the auditory brainstem response for detecting brainstem dysfunction in patients with cerebral palsy due to neonatal asphyxia.