The stimulus intensity modifies the blink reflex recovery cycle in healthy subjects and in blepharospasm

OBJECTIVE: The excitability of human brainstem interneurons is measured by the blink reflex recovery cycle and is abnormal in blepharospasm. We wondered whether the results of this paradigm depend on the stimulus intensity. METHODS: We investigated the blink reflex recovery cycle in 13 healthy control subjects and in 13 patients with blepharospasm (7 of them treated with botulinum toxin) using 4 levels of stimulus intensity (5, 12, 19 and 26 mA) and two interstimulus intervals (ISIs, 150 or 250 ms). RESULTS: In all groups the inhibition of the second R2 response was reduced with strong stimulus intensities: In controls, the inhibition of the second R2 decreased significantly (e.g. young controls, ISI 150 ms, from 89.6+/-15.6% at 5 mA to 21.9+/-49.7% at 26 mA, mean+/-standard deviation). In patients the R2 inhibition found at 5 mA was converted in an R2 facilitation at 26 mA, irrespective of the status of treatment. In addition, the patients' results at 5 mA did not differ significantly from the controls' results at 26 mA. CONCLUSIONS: The R2 inhibition and its sensitivity to detect abnormal interneuronal excitability depend on the stimulus intensity, which may act by modifying the excitability of the R2 interneurons.     

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.     

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.     

Blink reflex recovery curves in blepharospasm,torticollis spasmodica,and hemifacial spasm

R1 and R2 blink reflex responses to single and paired stimuli were investigated in 23 control subjects: 21 patients with blepharospasm (BSP), 20 patients with torticollis spasmodica (TS), and 23 with hemifacial spasm (HFS). For paired stimuli, we compared measurements of area and peak responses at two and three times R2 threshold. R1 and R2 indices were calculated as the average of the recovery values at 0.5-, 0.3-, and 0.21-s interstimulus intervals to test individual patients. Peak amplitude measurements at three times R2 threshold were optimal. The R2 index was abnormal in 67% of BSP patients, 37% of TS patients, and 50% of HFS patients on the affected side and 20% on the unaffected side. A normal R2 index in one third of patients with BSP may indicate that different pathophysiological mechanisms are involved in this type of focal dystonia. © 1996 John Wiley & Sons, Inc.     

Analysis of blink rate in patients with blepharospasm.

The blink rate (BR) during rest, conversation, and reading was assessed in 50 patients with blepharospasm (BS) and in 150 healthy subjects. BR at rest and during conversation was higher in patients with BS. Moreover, 76% of patients had BR higher at rest than during conversation, whereas in 74% of controls, BR was higher during conversation than at rest. The sensitivity and specificity of two parameters (value of BR at rest and pattern rest-BR higher than conversation-BR) in discriminating patients and controls were computed. The best fit was obtained with a rest-BR above 27 blinks per minute. When the two parameters were combined (rest-BR above 27 blinks per minute together with the pattern rest-BR higher than conversation-BR), we obtained a 92.3% sensitivity and a 82.0% specificity in discriminating between BS patients and controls. These findings indicate that specific features of BR can be associated with BS, suggesting that the analysis of BR might be helpful for the diagnosis of BS in early stages.     

脑干外脑卒中对瞬目反射的影响

目的　探讨脑干以上节段的病变对瞬目反射的影响。方法　对 42例脑卒中 1组和 2 0例脑卒中 2组患者于眶上切迹处以方波脉冲电刺激眶上神经 ,记录双侧眼轮匝肌的反应 ,测定刺激同侧的R1、R2 波和对侧的R2 波的潜伏期变化 ,同时对 2 4例正常对照组进行测定并对照分析。结果　脑卒中 1组瞬目反射各波潜伏期延长与对照组有显著性差异 ;脑卒中 2组瞬目反射各波潜伏期与对照组无显著性差异。结论　大脑半球病变对BR的影响是抑制性 ,与是否有中枢性面瘫、面部感觉障碍关系密切。     

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     

Feeding function, blink reflex and MRI in the severely handicapped

Blink reflexes were studied in 41 patients with severe handicaps, and were correlated with feeding problems and other lower brainstem symptoms such as drooling, an absent gag reflex and stridor. Ventrodorsal diameters of the pons and medulla oblongata on sagittal MRI were also studied in 29 of the cases. The patients were divided into three groups: tube feeding (25 cases), oral feeding (13 cases) and mixed feeding (3 cases). In the tube feeding group, all but three cases showed a prolonged or absent R1 component, and all cases showed prolonged or absent R2 and R2' components. These abnormalities were significantly more frequent in the tube than in the oral feeding group. The patients with drooling, stridor or an absent gag reflex more frequently showed prolonged or absent components than the patients without these symptoms. The brainstem size on MRI was not different between the tube and oral feeding group. These results suggest that the blink reflex, particularly its late components, is a useful indicator for evaluating feeding function and other lower brainstem functions.     

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.     

Partial restoration of blink reflex function after spinal accessory-facial nerve anastomosis.

Functional motor control requires perfect matching of the central connections of motoneurons with their peripheral inputs. It is not known, however, to what extent these central circuits are influenced by target muscles, either during development or after a lesion. Surgical interventions aimed at restoring function after peripheral nerve lesions provide an opportunity for studying this interaction in the mature human nervous system. A patient was studied in whom the spinal accessory nerve was anastomosed into a lesioned facial nerve, allowing voluntary contractions of the previously paralysed muscles. This procedure, in addition to replacing the facial neurons at peripheral synapses, allowed a new short latency trigeminospinal accessory reflex of the R1 blink reflex type to be demonstrated, implying that trigeminal neurons had sprouted towards spinal accessory motoneurons over a distance of at least 1 cm. These results show an unexpected influence of the periphery in remodelling central connectivity in humans. The motoneuronal excitability for this R1 reflex response was therefore studied to compare the convergent properties of facial motoneurons (normal side) with those of the spinal accessory motoneurons (operated side) using a classic double shock technique with variable interstimulus intervals (conditioning test stimulus). On the normal side, conditioning stimuli (to the ipsilateral or contralateral infraliminar supraorbital nerve) produced a clearcut facilitation of the R1 blink reflex when the interstimulus interval was 30-80 ms. By contrast, a similar procedure had no effect on the R1 blink reflex mediated via the trigeminal-spinal accessory reflex arc. These data indicate that despite the heterotopic sprouting of some axons from neurons in the XIth nucleus, motoneurons involved in the newly formed reflex arc remain totally inexcitable by other trigeminal afferents and seem unable to ensure a physiological functioning of the normal blink reflex. Thus the functional relevance of the recovered R1 blink response remains unclear.     

Maturation of the blink reflex in infants

The blink reflex was elicited in 50 children from birth to 3 years of age. In the awake state, the R1 response was always obtained; R2 responses, especially contralateral ones, were more difficult to elicit under 9 months of age. R1 latency and VIIth motor nerve conduction variations were a good witness of the peripheral nervous system maturation. The influence of the different states of waking and sleeping on these reflex responses was studied. These results and some of the mechanisms that underlie these changes are discussed.     

老年期抑郁症患者瞬目反射的研究

目的：探讨老年期抑郁症与瞬目反射（BR）的关系。方法：对34例老年期抑郁症患者及30名正常老年人进行BR检测,并对其中19例患者于治疗后进行复测。结果：患者组在左侧R2、R2′潜伏期以及右侧R2潜伏期指标显著高于对照组（P〈0．01）;患者组R1与R2、R1与R2′波潜伏期差值明显大于对照组。左侧R1与R2、R1与R2′,右侧R1与R2波潜伏期差值与对照组比较差异显著。19例患者治疗前后各项BR指标差异均无显著性。治疗前后HAMD变化与BR各项指标变化无显著相关。结论：老年期抑郁症患者存在BR异常,提示老年期抑郁症患者可能存在脑干功能障碍。     

Masseter reflex and blink reflex abnormalities in Chiari II malformation

Masseter reflex and blink reflex were evaluated in 64 patients with a myelomeningocele and Chiari II malformation. In 46 patients, no brainstem signs or symptoms were present. Brainstem dysfunction related to Chiari II malformation occurred in 18 patients. The masseter reflex was more frequently abnormal in the symptomatic than asymptomatic patients (P = 0.02). Although the blink reflex was similarly affected in the two groups of patients (P > 0.1), it was very sensitive, being abnormal in 83% of symptomatic and 65% of asymptomatic patients. Concomitant abnormality of masseter reflex and the late contralateral blink reflex component (R2c) was almost exclusively found in symptomatic patients and reached the highest significance in separating the two groups (P = 0.002).     

Influences of dopaminergic systems on the blink reflex

The effect of the anti-dopaminergic drug haloperidol (6 mg/day i.m. for 2 days) on the blink reflex elicited by electric stimulation of supraorbital nerves was investigated in 12 adult volunteers. A significant increase in amplitude of the early component (R1) of the reflex was observed. This increase disappeared within 5 days of stopping the drug. Possible neural systems which might be involved in these effects are considered.

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Sommario Su 12 volontari adulti, neurologicamente indenni, sono stati studiati gli effetti indotti dalla somministrazione di un farmaco dopaminolitico (aloperidolo, 6 mg/die × 2 giorni) sul riflesso di ammiccamento (blink reflex). Si è osservato un significativo aumento dell'ampiezza della componente precoce (R1) del riflesso, con un ritorno alla norma entro 5 giorni dalla cessazione della somministrazione del farmaco. Vengono discussi i possibili circuiti nervosi coinvolti negli effetti osservati.

     

脑卒中对瞬目反射的影响

目的 :探讨脑干以上节段的病变对瞬目反射 ( BR)的影响。方法 :共 3 0例脑卒中患者作了 BR检测。于眶上切迹处以方波脉冲电流刺激眶上神经。双侧下眼轮匝肌分别记录 ,刺激同侧所记录的两个波为 R1 、R2 ,刺激的对侧所记录到的一个波为 R'2 。结果 :( 1 ) BR2例正常、2 8例异常。 ( 2 )在这 2 8例 56侧中 BR各成分的异常率分别为 R1 :4 8.2 % ( 2 7/56)、R2 :69.6% ( 3 9/56)、R'2 :57.1 % ( 3 3 /56)。 ( 3 )两个或以上的 BR成分缺如者 9例 ,其中 5例有神志的改变、2例有失语、2例神志清楚。结论 :大脑半球病变对 BR总的影响是抑制性的。 BR的异常与病人的神志状况及有否失语密切相关 ,而与病变部位、是否有中枢性面瘫、偏瘫、面部感觉障碍以及检测的时间间隔均关系不大。