Blink reflex abnormalities in Tourette syndrome.

OBJECTIVE: Tourette syndrome (TS) is a not uncommon disorder which represents the most complex manifestation of the spectrum of tic disorders, with onset during childhood or early adolescence. There are no definitive tests for diagnosis of TS. The objective of this study has been to demonstrate whether neurophysiological abnormalities of the blink reflex can be observed in patients affected with TS and correlate with the severity of TS. METHODS: We enrolled 17 patients with Tourette syndrome, diagnosed according to DSM IV Diagnostic Criteria, and 10 healthy volunteers. Tic severity was assessed using a self rating scale (Tourette Syndrome Symptom List, TSSL) and examiner ratings (Yale Global Tic Severity Scale (YGTSS), and Tourette-Syndrome Global Scale (TSGS)). 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. RESULTS: We observed a mean duration of R2 significantly longer in the patient group than in the control group (P<0.01, Student t test), without any statistically significant differences of R1 and R2 latencies and of R1 amplitude between the patient group and the control group. Correlations between changes in clinical rating scores and R2 duration were tested by simple linear regression analysis, which has not demonstrated a significant correlation between TSSL scores, clinical rating scores (measured by TSGS and YGTSS) and duration of R2. CONCLUSIONS: A pattern as to excitability of the blink reflex can be a frequent abnormality in TS patients, not correlated with its severity.     

Ontogeny of spontaneous blinking and of habituation of the blink reflex.

Habituation of the blink reflex to glabellar percussion was examined in 164 infants and children from ages 2 days to 18 years and in 18 adults aged 18 to 50 years. Spontaneous blink rates were measured in 269 children and 179 adults. The mean number of glabellar taps required for habituation of the blink reflex increased from 2.7 (SD 1.2) at 0 to 2 months of age to a peak of 13.3 (SD 5.6) at age 3 to 4, remained at more than 10 until age 6, after which a rapid decline occurred, reaching the adult level of 2 to 5 blinks to habituation at age 12 years. The mean rate of spontaneous blinking was less than 2 per minute in early infancy and increased steadily during childhood up to age 14 or 15. The inverse relationship of spontaneous blink rate and number of blink reflexes to habituation in early childhood and in disorders of dopamine transmission suggests that spontaneous blink rate and habituation of the blink reflex reflect maturation and integrity of dopaminergic circuits in the brain.     

Maturation of blink reflex in children

The blink reflex was examined in 57 subjects aged from neonate to adult in the alert state. The ipsilateral late response (R2) was elicited in all subjects and considered most suitable to evaluate maturational changes of the blink reflex. In a few subjects older than 3 years and of adults, the ipsilateral early response (R1) was difficult to observe. The contralateral late response (R2') could not be obtained in 32% of neonates and infants. From the observation about developmental change of an interference pattern, a latency shortening of R2 and a latency difference between R2' and R2, the blink reflex in children may be considered as mature at no later than 5 years of age. In addition, the R2 latency tended to increase temporarily through 1 or 2 years from late infancy. The reflex circuit evaluated by the blink reflex in children may partially change its makeup after the early infantile period and is almost fully mature at no later than 5 years.     

Alterations in excitatory and inhibitory brainstem interneuronal circuits in fibromyalgia: Evidence of brainstem dysfunction

ObjectivePatients with fibromyalgia syndrome (FMS) perceive stimuli differently and show altered cortical sensory representation maps following peripheral stimulation. Altered sensory gating may play a causal role.MethodsBlink reflex, blink reflex excitability recovery, and prepulse inhibition of the blink reflex – representing brainstem excitability – were assessed in 10 female patients with FMS and 26 female healthy controls.ResultsUnconditioned blink reflex characteristics (R1 latency and amplitude, R2 and R2c latency and area-under-the-curve) did not differ significantly between patients and controls. Blink reflex excitability recovery was enhanced in patients versus controls at all intervals tested. Prepulses significantly suppressed R2 area and increased R2 latency in patients and controls. However, R2 area suppression was significantly less in patients than in controls (patients: to 80.0 ± 28.9%, controls: to 47.8 ± 21.7%). The general pattern of corresponding changes in R2c was similar.ConclusionsBlink reflex is normal, whereas blink reflex excitability recovery is enhanced and blink reflex prepulse inhibition is reduced in patients with FMS, suggesting functional changes at the brainstem level in FMS.SignificanceReduced blink reflex prepulse inhibition concurs with altered sensory gating in patients with FMS.     

Blink reflex abnormalities in chronic alcoholics

PURPOSE: The aim of the present study was to evaluate the efficacy of blink reflex as a method for obtaining early diagnosis of cranial nerve involvement in alcoholic patients. MATERIALS AND METHODS: The study was conducted on 30 male alcoholics with a mean age of 43 years. They had histories of alcohol abuse for at least 6 years (mean: 25). At the time of recording, they had undergone detoxification treatment for a mean of 27 days. RESULTS: R1 (early response), R2Y (second ipsilateral response), and R2C (second contralateral response) latencies in alcoholics were prolonged relative to controls and the differences were statistically significant (p < 0.02, p < 0.001, p < 0.001, respectively). According to the defined criteria, 40% of the patients had abnormal responses, and the most common abnormality was the unilateral prolongation of R1 (13%). CONCLUSION: Finding abnormal blink reflex responses in alcoholic patients has suggested that blink reflex testing is a useful method for the evaluation of subclinical cranial nerve involvement in alcoholic patients. Blink reflex testing may be useful in detecting early changes and in the follow-up of alcoholic disorder.     

Blink reflex alterations in diabetic patients with or without polyneuropathy

The main aim of this study is to evaluate the role of blink reflex for early diagnosis of cranial neuropathy in diabetic patients with or without polyneuropathy. Ninety-five diabetic patients were included in the present study for the evaluation of blink reflex. The diabetic patients were divided into two groups according to having diabetic neuropathy or not. Both R1, R2i and R2c latencies in all diabetic patients with or without polyneuropathy were prolonged relative to controls and the differences were statistically significant (p < .001). R1 latencies in diabetic patients with polyneuropathy were prolonged relative to diabetic patients without polyneuropathy and the differences were statistically significant (p < .001). These findings presumably reflect that facial nerve is severly involved in diabetic polyneuropathy. Finally blink reflex is of value in detection of clinically silent intraaxial brainstem functional abnormalities or extraaxial lesions in diabetic patients before peripheral neuropathy.     

Electrically and mechanically elicited blink reflexes in infants and children--maturation and recovery curves of blink reflex.

We studied the electrically and mechanically elicited blink reflexes in 2 groups of subjects, i.e., 237 newborn infants, 25-41 weeks of conceptional age, and 74 children, 1 month-12 years of age. In infants after 25 weeks of conceptional age we could usually induce the early response (R1) and ipsilateral late response (R2), while the contralateral late response (R2') of the electrical blink reflex became apparent after 33 weeks of conceptional age and the frequency of the appearance of R2' reached more than 60% after 38 weeks of conceptional age. After 7 months of age, R2' was usually observed. The R1 latency in full-term newborns was close to adult values, while the R2 and R2' latencies reached adult values at 7-12 years. After 1 year of age the latency of the R2 mechanical blink reflex had a tendency to be shorter than that of the electrical blink reflex. Under 35 weeks of conceptional age, the recovery curves of the blink reflex were considerably different from those of full-term infants, and premature infants showed little or no evidence of inhibition. These results indicate the absence of inhibitory interneurones in premature infants.     

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.     

The three responses of the blink reflex in adult and juvenile migraine

Recent theories about migraine pathogenesis have emphasized the role of the trigeminal system in the pathogenesis of migraine attacks (Moskowitz, 1997). The blink reflex (BR) could be a suitable method to evaluate the trigeminal system in migraine, as it is generally elicited by stimulation of the trigeminal ophthalmic division (Kimura et al., 1967), involved in migraine attacks. Sixty one adult and 15 juvenile migraine without aura subjects were selected, in order to evaluate the BR features, including the subjective perceptive and pain thresholds and the R1, R2 and R3 components intensity thresholds and amplitudes. The electrophysiological procedure was carried out during the pain free phase. The findings were compared with those of 28 healthy controls, 18 adults and 10 children. In both adult and juvenile migraine sufferers an early appearance of the R3 response at almost the R2 threshold was observed in comparison with age-matched controls. Unfortunately, the anatomic and physiologic organization of the R3 component is uncertain: its early onset could suggest a dysfunction of the inhibitory control system on the trigeminal networks, which may predispose to migraine attacks.     

The orbicularis oculi response after hemispheral damage.

The corneal and blink reflexes were evaluated in 20 normal subjects and in 30 patients with motor deficits secondary to unilateral hemispheral lesions of vascular origin. In the normal population there were no differences between subjects below and subjects above 50 years of age. In the patients the reflex evoked by electrical stimulation of the cornea of the clinically affected side was depressed in 24 out of 30 cases. The depression mainly affected the afferent branch of the circuit, which triggers both homolateral and contralateral orbicularis oculi discharge (afferent abnormality). In three cases the depression was exerted concomitantly on the efferent branch (afferent and efferent abnormality) and only in one case was it limited to the efferent branch (efferent abnormality). The late R2 component of the blink reflex was depressed in 15 out of 30 patients. The early R1 component was slightly facilitated on the affected side. The changes of the corneal reflex and of the R2 component of blink reflex were similar, but the blink reflex had a greater safety factor. The patients with an abnormal corneal reflex had more extensive damage than had the patients with normal corneal response, as shown by computer tomography, but the site of the lesion was comparable in the two groups. Conduction through the brain stem circuits mediating the orbicularis oculi response is normally under pyramidal facilitatory influences while facial motoneurons are subjected to pyramidal inhibition. After pyramidal damage the transmission of impulses in the brain stem was slowed down, ultimately to a degree that abolished the reflex. Removal of pyramidal inhibition on facial motoneurons is probably the basis of the slight facilitation of the R1 component of the blink reflex.     

Effect of experimental posterior temporalis muscle pain on human brainstem reflexes.

OBJECTIVE: To study the modulation of jaw-stretch and blink reflexes by experimental posterior temporalis muscle pain. METHODS: Thirty healthy volunteers (15 males, 25.5+/-0.6 years and 15 females, 27.4 +/- 1.2 years) were included. Short-latency stretch reflex responses were evoked in the masseter and temporalis muscles by fast stretches (1 mm displacement, 10 ms ramp time) and the blink reflexes were evoked by painful electrical pulses (0.5 ms duration), delivered by a concentric electrode placed on the left lower forehead close to the supraorbital foramen before, during and 15 min after a period with experimentally induced muscle pain. RESULTS: The normalized peak-to-peak amplitude of the stretch reflex in the painful temporalis was significantly higher during pain in both males and females compared with pre- and post-pain conditions (P < 0.004). The R2 root mean square (RMS) of the blink reflex decreased significantly during muscle pain as compared to the pre-pain (P < 0.03) in both males and females. CONCLUSIONS: The present results indicated that experimental posterior temporalis muscle pain facilitates the jaw-stretch reflex, whereas the nociceptive specific blink reflex is inhibited. SIGNIFICANCE: Present study suggested that these reflexes are suitable models for probing pontine and medullary pain processing.     

Variability of the blink reflex in patients with migraine

Background and purposeSensitization of brainstem trigeminal nuclei and activation of the trigeminovascular system are thought to play an important role in migraine. The blink reflex has become a valuable tool for investigating trigeminal nerve function. The aim of the study was to assess the differences in electrophysiological examinations of the trigeminal nerve (blink reflex) in a group of patients with migraine in comparison with a healthy control group.Material and methodsThe examination was conducted among 58 patients. Patients were diagnosed in the Polyclinic or hospitalized in the Department of Neurology of Warsaw Medical University in Bielański Hospital. The study group included 29 patients suffering from migraine (diagnosed according to the International Classification of Headache Disorders, 2^nd edition) and 29 patients without headaches served as controls. All patients underwent neurological examination and magnetic resonance imaging to identify organic disorders. The blink reflex was tested among all patients in accordance with electrophysiological laboratory standards.ResultsThe latency of the R1 response was significantly shorter among patients with migraine. The latency of R2 and R2’ responses was similar in patients and controls. A significant inverse correlation was observed between latency of R2 and R2’ responses and frequency of migraine attacks.ConclusionsThe inverse correlation between the frequency of attacks and the latency of R2 and R2’ responses of the blink reflex confirms the abnormal eaxcitability induced by the high frequency of migraine attacks.     

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.     

Reflex studies and MRI in the restless legs syndrome

Brainstem and spinal pathways of untreated patients with idiopathic restless legs syndrome (RLS) were examined using magnetic resonance imaging (MRI), blink reflex, first and second exteroceptive suppression (ES1, ES2) of temporalis muscle, and H reflex. MRI of 25 patients elicited no structural lesions beyond age-related atrophy or white matter lesions on proton density- and T2-weighted coronal and axial images. All patients showed a normal latency of the soleus H reflex (mean·SD latency=31.22·2.81 ms) and the H/M ratio was 48·17%. The duration and onset latency of the direct and indirect blink reflex responses were normal in all patients compared with those of controls (p>0.5). There was no significant difference in ES1 and ES2 latencies or duration between patients and controls (p>0.5). These results suggest that the etiology of RLS symptoms does not involve structural lesions.     

Blink reflex in young children with medullary kink in Chiari malformation.

We studied the blink reflex (especially the late components ipsi- and contralateral to stimulation site, R2 and R2') in 17 patients under 6 years of age; 12 with Chiari malformation, 1 with Dandy-Walker syndrome and 4 with brainstem tumor. We investigated the correlation between the R2 or R2' and neuro-image findings. Out of various features of the brainstem lesion revealed by MRI or CT examinations, the medullary kink characteristic in Chiari malformation was most responsible for abnormality of R2 and R2'. In addition, the fact that the disturbance of R2 and R2' in patients with Chiari malformation was more apparent in younger children than older ones confirms the intrinsic vulnerability of the blink reflex in the younger age groups as noted in normal children.     

Trigeminally induced startle in children with hyperekplexia.

To determine the physiological features of startle reactions in children with hereditary hyperekplexia, motor responses to auditory and trigeminal stimulation were investigated in 2 patients and 3 control subjects by means of multiple surface electromyographic recordings. The pattern of motor activation in auditory startle was similar in the two groups, although the responses in the patients were increased in terms of the extent of the responses. In the patients, nose taps elicited two separate responses in various muscles. The initial, short-latency response was often elicited in all the muscles examined. This reflex was similar to the R1 component of the electrical blink reflex. In addition, the early reflex was immediately followed by the second response, which also appeared widely and was similar to R2 of the blink reflex. Taps on the supraorbital nerve elicited multiple startle patterns consisting of these two responses, although generalization was infrequent. In the control subjects, these responses were elicited in a few muscles. In the hyperekplectic children, both the early and second responses to trigeminal stimulation were increased, in addition to the audiogenic reflex. It was suggested that enhancement of these responses occurred due to hyperexcitability in the brainstem reticular formation in our patients.     

Cyclic alterations of blink reflexes: an EEG and EMG study during wakefulness and sleep.

Studies of the blink reflex were undertaken in twelve normal subjects during wakefulness and different sleep stages. The early R1 and the late R2 components of the reflex were analyzed. R1 was present in only one subject during stage I sleep and subsequently disappeared in stage II to IV. In all subjects, R2 was gradually diminished and totally disappeared during stage IV. During the REM stage, R1 was seen in only four-out-of-twelve subjects but all R2 returned. Alterations of R1 and R2 of the blink reflex during different sleep stages suggest that the underlying mechanism includes both supranuclear and infranuclear activities. Our finding strengthens further the notion of dual hyponogenic mechanisms for sleep.     

Development of the blink reflex during the 1st 3 years of a child's life

The blink reflex was elicited in 42 awake and quiet children from birth to 3 years of age. The R1 ipsilateral reflex response was always recorded. Its latency decreased significantly during the first 6 months of life whereas the VIIth nerve motor conduction velocity increased markedly; its threshold stimulus was lower in children after 1 year of age. R2 responses, especially contralateral ones, were sometimes absent in infants under 9 months of age; beyond that age, they were constant and bilateral. The ipsilateral R2 latency response diminished during the first 6 months of life, and the R2 reflex threshold became lower in infants above 1 year of age. When elicited after crying, in 22 children, the reflex components were facilitated; R1 response occasionally appeared bilaterally, its amplitude increased and its threshold was lower. During REM sleep, in 12 children, the reflex responses were similar to those recorded during quiet wakefulness. On the contrary, non-REM sleep recorded in 12 children markedly depressed the reflex responses; this inhibition was more pronounced for R2 responses.     

A new method to increase nociception specificity of the human blink reflex.

OBJECTIVE: The medullary R2 response of the blink reflex can be elicited by innocuous and noxious stimuli. The purpose of this study was to elicit a nociception specific R2 response with a new surface electrode. METHODS: In 10 healthy subjects the blink reflex was elicited using a standard (10-15 mA) and a new concentric surface electrode type (0.6-1.6 mA) which produces a pin-prick-like pain. RESULTS: After topical local anaesthesia with lignocaine/prilocaine R1 was unchanged, R2 was attenuated by 12% after standard stimulation but was almost abolished (-91%) with the new electrode type. CONCLUSION: Stimulation with low stimulus intensities but electrode-dependent high current density allows preferential depolarization of superficial nociceptive A-delta fibres. This new method is less traumatic than others and is useful in the study of trigeminal nociception.     

Blink reflex in patients with hemispheric cerebrovascular accident (CVA). Blink reflex in CVA

A blink reflex consists of an early unilateral component, R1, and a late bilateral component, R2. During an acute phase of hemispheric cerebrovascular accident, R1 and R2 were abnormal in 30 and 50 of 66 patients, respectively. Paired stimuli usually corrected R1 but not R2, which was profoundly suppressed. The discrepancy between polysynaptic R2 and oligosynaptic R1 indicates a greater disfacilitation at the level of interneurons than at the motoneuron, which serves as the final common path. Abnormality of R2 occurred bilaterally with stimulation on the affected side of face and contralaterally after stimulation on the normal side in 31 patients. This finding suggests a diffuse loss of internuncial excitability, contralateral to the hemispheric lesion. Changes of R2 implicated the brainstem pathways forming the afferent and efferent arc of the reflex in 7 and 8 patients, respectively. The remaining 4 comatose patients had no R2 irrespective of stimulus sites. Clinical localization of the hemispheric lesion showed no consistent correlation with the type of blink reflex abnormalities. The CT scans revealed widely scattered changes in 29 patients with abnormal blink reflex but with a tendency to overlap in the inferior Rolandic area. This contrasted with conspicuous sparing of the inferior post-central region in 10 patients with normal blink reflex. These findings suggest the presence of crossed facilitation to this reflex from wide areas of the cortex but most prominently from the sensory representation of the face.