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.     

Corneal and blink reflexes in Parkinson's disease with "on-off" fluctuations

In 13 patients with Parkinson's disease and "on-off" fluctuations and in a control group, the electrically evoked blink (R1 and R2 component) and corneal reflexes (CR), the habituation of the glabellar reflex, and the blink rate were studied. Latency, amplitude, and recovery cycle of R1 was normal. CR latency, but not R2 latency, was significantly shorter in patients than in normal subjects. R2 recovery cycle, but not CR recovery cycle, was facilitated in "off" patients in comparison to normal subjects. CR and R2 duration was longer in "off" than in "on" patients. R2 recovery cycle became similar to that of normal subjects after fluctuation from "off" to "on" period, but CR recovery cycle varied only slightly. The habituation of the glabellar reflex and the blink rate were decreased in "off" patients. These findings indicate that the enhanced excitability of R2 is related to the central dopamine activity levels. The differences between the recovery cycles of CR and R2 may be explained with the smaller number of interneurons subserving CR than R2 circuit. The shorter latency of CR, but not of R2, both in "on" and "off" patients, may suggest that in Parkinson's disease basal ganglia exert a different control of incoming sensory input transmitted via beta and delta fibers.     

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.     

Fear conditioned potentiation of the acoustic blink reflex in patients with cerebellar lesions

OBJECTIVE: To investigate whether the human cerebellum takes part in fear conditioned potentiation of the acoustic blink reflex. METHODS: A group of 10 cerebellar patients (eight patients with lesions involving the medial cerebellum, two patients with circumscribed lesions of the cerebellar hemispheres) was compared with a group of 16 age and sex matched healthy control subjects. The fear conditioned potentiation paradigm consisted of three phases. During the first, habituation phase subjects received 20 successive acoustic blink stimuli. In the subsequent fear conditioning phase, subjects passed through 20 paired presentations of the unconditioned fear stimulus (US; an electric shock) and the conditioned stimulus (CS; a light). Thereafter, subjects underwent the potentiation phase, which consisted of a pseudorandom order of 12 trials of the acoustic blink stimulus alone, 12 acoustic blink stimuli paired with the conditioned stimulus, and six conditioned stimuli paired with the unconditioned stimulus. The EMG of the acoustic blink reflex was recorded at the orbicularis oculi muscles. The potentiation effect was determined as the difference in normalised peak amplitude of the blink reflex evoked by pairs of CS and acoustic blink stimuli and evoked by the acoustic stimulus alone. RESULTS: In the habituation phase, short term habituation of the acoustic blink reflex was preserved in all cerebellar patients. However, in the potentiation phase, the potentiation effect of the blink reflex was significantly reduced in patients with medial cerebellar lesions compared with the controls (mean (SD) potentiation effect (%), patients: -6.4 (15.3), controls: 21.6 (35.6)), but was within normal limits in the two patients with lateral lesions. CONCLUSIONS: The present findings suggest that the human medial cerebellum is involved in associative learning of non-specific aversive reactions-that is, the fear conditioned potentiation of the acoustic blink reflex.     

The blink reflex in "chronic migraine".

OBJECTIVES: Activation of the trigeminovascular system and sensitisation of brainstem trigeminal nuclei are thought to play an important role in migraine. The aim of this study was to investigate the blink reflex and its habituation in patients with "chronic migraine". METHODS: We studied 35 patients suffering from "chronic migraine" (IHS classification criteria) outside and during a spontaneous attack, and 35 control subjects. An EMG device with a specific habituation test program was used to elicit and record blink reflex responses and to randomly repeat stimulations at different time intervals so as to induce habituation. RESULTS: The R(1) and R(2) latencies, amplitudes and areas of the basal blink reflex were similar in patients studied both outside and during an attack as well as in control subjects, whereas the blink reflex habituation responses were markedly reduced in patients studied outside an attack. The percent changes in the R(2) areas from the baseline values, obtained when stimuli were delivered at time intervals of 10, 5, 4, 3, 2 and 1s, were statistically different (p<0.01-p<0.001) from those of the same patients studied during a migraine attack and of those of control subjects. There was a significant correlation between decreased habituation of the blink reflex and a higher frequency of attacks. The stimulus intensities of the blink reflex (multiples of the detection threshold intensities) were significantly lower (p<0.001) on the side affected, or more severely affected, by headache in patients studied during a migraine attack. CONCLUSIONS: The decreased habituation of the blink reflex outside an attack reflects abnormal excitability in "chronic migraine", which normalizes during the attacks. The inverse correlation between the frequency of attacks and habituation responses confirms the abnormal excitability induced by the high frequency of attacks. Central sensitisation mechanisms (allodynia) may explain the lower detection thresholds observed on the side affected by headache in patients during the attacks. SIGNIFICANCE: The blink reflex and its habituation may help shed light on the subtle neurophysiological changes that occur in migraine patients between and during attacks.     

Developmental changes in electrically elicited blink reflex in infancy and childhood

Developmental changes in electrically elicited blink reflex (BR) in 118 normal subjects, aged from 32 weeks of conceptional age to 14 years of age. During the waking state, R1 and bilateral R2 responses were always elicited. The latency of R1 shortened rapidly during the neonatal period, reaching the adult value at 3 months of age. The latency of R2 and contralateral R2 (CR2), which were elicited synchronously after 3 years of age, shortened slowly during childhood and reached the adult value at 6 years of age. The conduction indexes of R1, R2 and CR2, which were calculated as head circumference/latency (m/sec), increased rapidly during the neonatal period and reached the adult values at 6 years of age. The influence of NREM sleep on BR in neonates was different from those in infants and children. While BR of neonates in NREM sleep showed similar to that seen in wakefulness, BR of infants and children after one month of age was suppressed during NREM sleep. BR pattern in NREM sleep in infants and children after 6 months of age was similar to that seen in adults.     

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.     

Effects of lisuride on blink reflex habituation in Parkinson disease

The blink reflex presents a tendency to habituation (a gradual diminution of the amplitude of the response during repetitive stimulation). Electromyographic analysis of this reflex makes it possible to quantify this phenomenon. A lack of the habituation of the blink reflex is a typical feature of Parkinson disease. L-Dopa and amantadine, but not anticholinergic drugs, are able to partly reverse these abnormalities in blink reflex habituation to a normal pattern. Lisuride, a dopamine agonist with serotoninergic activity, has been recently proposed as antiparkinsonian agent. In our study we observed that lisuride has a positive effect on blink reflex habituation in Parkinson disease. A good correlation between the improvement of this electrophysiological parameter and clinical akinesia was seen. Mechanisms underlying the therapeutic effect of lisuride are complex, but this drug usually has a postsynaptic effect on D2 receptors. Our data suggest that these receptors play an important role in blink reflex habituation.     

Eye blink and schizophrenia: psychosis or tardive dyskinesia?

The author found abnormalities of ocular movement including abnormal blink rate and blink reflex to glabellar tap in 34 of 44 medication-free schizophrenic patients. It is not clear whether these signs represent part of the pathology of schizophrenia or result from withdrawal of neuroleptic treatment.     

Electrophysiological evidence for a neurohormonal dependence in the changes of the late glabellar response in man.

In 19 normal adults reserpine administration induced significant changes in the parameters of the second glabellar response (R2): shortening of the latency and duration; decrease of the excitability threshold and complete blockade of the physiological habituation of R2 to the electrical and mechanical stimulation. No changes in the first response (R1) were observed. All the R2 changes disappeared within about 3 days of drug administration. The Parkinson-like effect of reserpine on the glabellar reflex is discussed in the light of a neurohormonal hypothesis in the control of the polysynaptic pathways biasing R2.     

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.     

The relationship between eye-winking tics, frequent eye-blinking and blepharospasm.

A family is reported in which three generations were affected with eye-winking tics and/or blepharospasm. The proband developed eye-winking tics in childhood and then developed excessive blinking progressing to blepharospasm by the age of 21 years. His mother presented with Meige's syndrome and spasmodic torticollis at the age of 59 years; his uncle had blinked excessively from his early forties. His eldest son developed an eye-winking tic with facial grimacing at the age of 8 years, and in another son, a self-limiting period of eye-blinking occurred at the age of 4 years. The recovery cycle of the blink reflex was abnormal in all three generations. Three other children with eye-winking tics have a parent or close relative with frequent eye-blinking or blepharospasm. Five patients with adult-onset blepharospasm or Meige's syndrome are also described who had excessive eye-blinking dating back to childhood. It is suggested that eye-winking tics, frequent blinking and blepharospasm may share common pathophysiological mechanisms; the clinical expression may be age-related.     

Decreased habituation of the R2 component of the blink reflex in migraine patients.

OBJECTIVE: Activation of the trigemino-vascular system as well as of brainstem trigeminal nuclei are thought to play an important role in migraine. The aim of this study was to investigate the habituation phenomenon of the blink reflex in 30 headache-free migraine patients and 30 control subjects. METHODS: An electromyographic device with a specific habituation test program was used to elicit and record blink reflex responses on both the right and left sides, and to randomly repeat the stimulations at different time intervals in order to induce habituation. RESULTS: Whereas the R1 and R2 latencies, amplitudes and areas in the basal assessment were similar in patients and control subjects, the blink reflex habituation responses were markedly reduced in migraine patients who had a migraine attack within 72 h after testing (group A). In these patients, the differences between the R2 areas, obtained when stimuli were delivered at subsequent time intervals ranging between 10-5, 5-4, 4-3 and 3-2 s, were statistically different (P<0.001) from those of the patients who had a migraine attack after a longer time interval (group B) and control subjects. CONCLUSIONS: Our data suggest that the brainstem pathways involved in the blink reflex may be activated in the premonitory phase of migraine attacks, probably through mechanisms that involve dopaminergic function.     

Habituation of the blink reflex: computer assisted quantitative analysis

The electrically evoked blink reflex (BR) was elicited in 20 healthy volunteers, varying the stimulus interval by a computer JN 110. Latencies, amplitudes, reflex duration and reflex areas of early and late components of the BR were analysed by a computer program testing the signal-to-noise ratio, the response configuration and frequency distribution. Changes in habituation related to the stimulus interval can be illustrated best by the progressive diminution of R2 areas. Computing the habituation in relation to the stimulation frequency by a standardized program seems to be a quantitative method to assess habituation in various diseases and during treatment studies.     

Re-evaluation of short latency somatosensory evoked potentials (P13, P14 and N18) for brainstem function in children who once suffered from deep coma

One of the major clinical features of brain death is deep coma. Therefore, we re-evaluated retrospectively electrophysiological examinations of brainstem function in about 31 children who had once suffered from deep coma in order to reveal its pathophysiological characteristics. The patient age at coma ranged from 1 month to 10 years (mean 2 years 1 month). The electrophysiological examinations were performed, including any of short-latency somatosensory evoked potential (SSEP), brainstem auditory evoked potential (BAEP) and blink reflexes. We first compared results between the fair and poor prognostic groups, and then re-evaluated SSEP results on a few severely impaired patients with persistent vegetative state (PVS). Subsequently, SSEP clarified more specific findings for a deep coma condition than BAEP and blink reflex. A lack of P14, N18 and N20, and an amplitude reduction or vagueness of P13 in SSEP in these children strongly suggested high risk in their future neurological prognosis. In conclusion, electrophysiological examinations, especially SSEP (P13, P14 and N18), might be very useful in obtaining a long-term neurological prognosis after deep coma in children.     

Blink reflex measurement of effects of trichloroethylene exposure on the trigeminal nerve.

Trichloroethylene (TCE) exposure is known to have specific toxic effects on cranial nerves, the trigeminal nerve (V) in particular. The electrophysiological measurement of the blink reflex (BR) can quantify latency changes in the Vth and VIIth cranial nerve reflex arc. Prior study looked at the blink reflex measurement in a community group exposed to TCE in their drinking water. This study evaluated the use of the electrophysiologic blink reflex as an indicator of neurotoxic effects of TCE in occupationally exposed workers. The BR was tested in individual cases with documented histories of exposure to known chemical neurotoxins including TCE (n = 18). When compared with the nonexposed laboratory control values (n = 30), the subjects with a significant history of TCE exposure demonstrated the most prolonged latencies (greater than or equal to 3.0 SD above the nonexposed group mean) in the R1 component of the blink reflex measurement. The electrophysiological study of the blink reflex has application in assessing TCE exposure and in documenting the neurotoxic effects of that exposure on trigeminal nerve functions in humans.     

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.     

Disturbances of ocular movements and blinking in schizophrenia.

Neurological examination and electroencephalograms and electro-oculograms, recorded by telemetry, from unmedicated patients with acute and chronic schizophrenia demonstrate a number of abnormalities of extraocular movement including staring, abnormal blink rate, absent glabellar reflex, and increase in horizontal eye movements. As potential clues to the pathophysiology of schizophrenia, these disturbances are analysed in relation to anatomical substrate and dopamine modulation of ocular movement, rapid eye movement sleep, and the neurological disorders in which similar disturbances of ocular movement occur.     

Two-year prospective follow-up of children with a prepubertal and early adolescent bipolar disorder phenotype

OBJECTIVE: Longitudinal outcomes of bipolar disorder with onset in the late teenage years or in adulthood have been reported, but little is known about the natural history of childhood-onset mania. This study sought to provide rates and predictors of recovery and relapse in children with a prepubertal and early adolescent bipolar disorder phenotype. METHOD: Eighty-nine consecutively ascertained outpatient subjects (mean age=10.9 years [SD=2.7]) received comprehensive research assessments, including separate interviews of mothers about their children and of children about themselves, at baseline and at 6, 12, 18, and 24 months after baseline. The study phenotype required DSM-IV mania with elation and/or grandiosity as one criterion to distinguish the study phenotype from a diagnosis of mania based on criteria overlapping with those for attention deficit hyperactivity disorder and to ensure that subjects had at least one of the two cardinal features of mania (i.e., elation and/or grandiosity). Subjects were treated by their own community practitioners. RESULTS: The proportions of subjects who recovered from mania and who relapsed after recovery were 65.2% and 55.2%, respectively. The mean time to recovery was 36.0 weeks (SD=25.0). Relapse occurred after a mean of 28.6 weeks (SD=13.2). Living with an intact biological family significantly predicted rate of recovery, and a low level of maternal warmth significantly predicted rate of relapse. CONCLUSIONS: The relatively poor outcomes of these subjects may be related to their phenotypic resemblance to severely ill adults with bipolar disorder who have mixed mania, continuous rapid cycling, psychosis, and treatment-resistant psychopathology. A lower level of effectiveness of mood stabilizers in children cannot be ruled out. Although the significance of maternal warmth as a predictor is consistent with reports in adult mania, the significance of intact family as a predictor may be unique to childhood mania.     

Eyelid movements during blinking in patients with Parkinson's disease.

We examined eyelid movements during spontaneous, voluntary, and trigeminal reflex blinks in 16 patients with mild to moderate Parkinson's disease (PD) off medication and 14 controls. Voluntary and reflex blink amplitudes tended to be smaller than normal for PD patients, whereas eyelid kinematics (amplitude-maximum velocity relationship) for all three blink types were normal. Spontaneous blink rate was less than normal for 10 patients and abnormally high for 6 patients. A significant positive correlation between spontaneous blink amplitude and blink rate was found. These observations suggest that PD modifies the gain of a premotor blink circuit shared by spontaneous, voluntary, and reflex blinks.