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.     

Group I nonreciprocal inhibition in primary restless legs syndrome

Electrophysiological investigations of restless legs syndrome (RLS) have found spinal circuits impinging on motoneurones. We evaluated the H reflex threshold, latency, the Hmax/Mmax ratio, and the short latency autogenic inhibition in 7 patients with RLS and 10 age‐matched controls by testing the excitability changes in soleus H reflex Ib interneuron function. A significant reduction in Ib inhibition at 4 (P = 0.043), 5 (P = 0.007), and 6 ms (P = 0.001) of H reflex conditioning interstimulus interval was found in RLS patients. Data support the hypothesis that altered group I nonreciprocal inhibition is implicated in enhancing the spinal circuitry excitability of RLS, and are consistent with the view of an abnormal supraspinal drive to spinal interneurons in RLS. © 2007 Movement Disorder Society     

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.     

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.     

Electrophysiological findings in patients with restless legs syndrome

BackgroundRestless legs syndrome (RLS) manifests as an urge to move the body to relieve the discomfortable sensations, primarily when resting, sitting, laying down, or sleeping. Diagnosis of RLS relies on clinical criteria, and the immobilization test was the only instrumental tool with equivocal results.ObjectivesTo assess different electrophysiological findings in patients with RLS, and compare the diagnostic values of these parameters in the diagnosis of RLS.Methods30 patients with primary RLS and 30 controls who were matched for age and gender were studied. Participant's demographics, laboratory findings, and electrophysiological test, namely nerve conduction studies (NCS), cutaneous silent period (CSP), H reflex and sympathetic skin response (SSR), F-wave latency, amplitude, F-wave duration (FWD), and the ratio between FWD and duration of the corresponding compound muscle action potential (FWD/CMAPD) were analyzed.ResultsNone of the patients showed altered NCS data. FWD of upper (12.37 ± 2.77 ms) and lower limb (21.71 ± 5.24 ms) were significantly longer in patients. Also, FWD/CMAP duration of the upper (1.03 ± 0.2) and lower limb (2.02 ± 0.55) was longer in patients. Likewise, they exhibited delayed CSP latency from TA (110.62 ± 13.73 ms) and APB (77.35 ± 12.16 ms) whereas the CSP duration from TA and APB was decreased (37.36 ± 11.59 ms; 42.55 ± 7.97 ms, respectively). The SSR latency was not different, and right-sided H reflex amplitude (5.07 ± 3.98 mV) and H/M ratio (0.65 ± 1.81) were significantly increased in the patient group.ConclusionThe data suggest that there may be a dysfunction of the inhibitory/excitatory circuits at a spinal level; and no pathology in the peripheral nerves. The unilateral difference of H reflex amplitude and H/M ratio may suggest asymmetrical central inhibitory dysfunction. Further prospective studies with larger cohorts are now needed to evaluate the pathophysiology of RLS with different neurophysiological assessment tools.     

Blink reflex in facial-hypoglossal anastomosis

Summary The blink reflex was investigated in two patients after a facial-hypoglossal anastomosis had been performed. In each case the first component of the blink reflex could be demonstrated with normal latency on the operated side after ipsilateral supraorbital stimulation. These findings give further evidence that the first component of the blink reflex is not monosynaptic in nature. The second component of the blink reflex was distinctly retarded in the first case and was not seen at all in the second case. The second component of the blink reflex is influenced strongly by alteration of the intrabulbar and efferent part of the reflex circuits; it shows some correlation with voluntary motor activity.Stipendiary of the Humboldt Foundation.     

Effects of Monotherapy and Polytherapy on the Blink Reflex in Epileptic Patients

We performed the blink reflex (BR) in 20 normal volunteers, 13 epileptic patients receiving antiepileptic drug (AED) monotherapy, and 13 epileptic patients receiving AED polytherapy. Comparison of R1, ipsilateral and contralateral R2 and VIIth nerve latencies in the three groups showed no statistically significant differences in R1 and VIIth nerve latencies among the three groups. There were statistically significant differences between the polytherapy group and the monotherapy and control groups in comparisons of ipsilateral and contralateral R2. There were no significant differences between the monotherapy group and the control group for ipsilateral and contralateral R2. We hypothesized that AED polytherapy might interfere with synaptic transmission in the polysynaptic pathway of the blink reflex, prolonging the latency of R2. These results provide further evidence of the pathophysiologic effects associated with polytherapy in epileptic patients.     

No correlation between number of MRI-evident lesions in cerebrum and the soleus stretch reflex in multiple sclerosis patients

The aim of the study was to investigate if the stretch reflex of the soleus muscle was useful in quantifying upper motor neuron lesions. The soleus stretch reflex was recorded in 10 healthy subjects and 20 patients with active relapsing-remitting multiple sclerosis and correlated to the number of MRI lesions in cerebrum and clinical scores (expanded disability status scale and regional functional scoring system). The short latency stretch reflex was elicited by rotating the left ankle joint 4 degrees with a rise time in the interval of 40-640 ms. The amplitude of the stretch was larger in multiple sclerosis patients being 88.5 microV in patients and 12.8 microV in controls, P = 0.007. The sensitivity of the stretch reflex expressed as the slope of the best linear fit was increased in MS patients to 2.6 microVs/degree compared with 0.6 microVs/degree (0.1-2.2) in controls, P = 0.009. There was no correlation between amplitude of the stretch reflex and number of MRI lesions (r = -0.03). In conclusion, the soleus stretch reflex might be useful to quantify spasticity but is not useful in detecting dysfunction of upper motor neurons in MS.     

Topodiagnostic value of blink reflex R1 changes: a digital postprocessing MRI correlation study

The aim of the study was to investigate the relation of the blink reflex R1 arc to known anatomical brainstem structures. Acute vascular brainstem lesions as identified by magnetic resonance imaging (MRI) of patients with isolated R1 pathology were superimposed into a stereotactic anatomical atlas using a new method of digital postprocessing. Isolated acute brainstem lesions were documented by diffusion-weighted MRI in 12 of 24 patients with unilateral R1 pathology. The lesions were located in the ipsilateral mid- to lower pons. In three patients only, the lesion had partial contact with the principal sensory nucleus of the trigeminal nerve (PSN) on at least one level. In two patients, the lesion involved the medial longitudinal fasciculus. Most lesions were located medially and ventrally to the PSN on transverse slices. Our results underline the high localizing value of changes in the R1 component of the blink reflex in patients with ipsilateral pontine functional deficits. Although available physiological evidence suggests that the R1 component of the blink reflex traverses an oligosynaptic pathway, this MRI study does not support the view that synaptic transmission in the PSN subserves R1. The reflex arc probably descends more medially and ventrally on its course to the facial nucleus.     

瞬目反射及脑干听觉诱发电位对脑干梗死疗效的评价

目的探讨瞬目反射和脑干听觉诱发电位对脑干梗死患者疗效的评价作用。方法40例经临床症状、体征定位于脑干髓内并经头部MRI检查明确诊断的脑干梗死患者(脑桥梗死31例、中脑梗死4例和延髓梗死5例),分别计算治疗前后瞬目反射各成分的平均潜伏期;观察脑干听觉诱发电位波形及各波潜伏期、峰间期的变化。结果经治疗后40例患者临床症状及体征均有不同程度改善,治疗前后瞬目反射各成分平均潜伏期之间差异无统计学意义(P>0.05);3例脑桥梗死患者R1波恢复正常,临床基本痊愈。治疗前后脑干听觉诱发电位各波潜伏期及峰间期比较,差异亦无统计学意义(P>0.05);治疗后中脑梗死及脑桥梗死患者各有2例恢复正常,临床症状明显好转。结论瞬目反射与脑干听觉诱发电位均能敏感地反映脑干功能的变化,与临床表现具有一致性,但在发病15d内大部分病例的电生理活动不能恢复正常。     

Blink reflex R2 changes and localisation of lesions in the lower brainstem (Wallenberg's syndrome): an electrophysiological and MRI study

OBJECTIVES: Pathways of late blink reflexes are detected by high resolution MRI. Electronically matched stroke lesions superimposed to an anatomical atlas show the suspected course. METHODS: Fifteen patients with infarction of the lower brainstem, MRI lesions and electrically elicited blink reflexes were examined. The involved structures in patients with R2 and R2c blink reflex changes were identified by biplane high resolution MRI with individual slices matched to an anatomical atlas at 10 different levels using digital postprocessing methods. RESULTS: The blink reflexes were normal in five of 15 patients (33%) and showed loss or delay of R2 and R2c to stimulation ipsilaterally to lesion (R2-i and R2c-i) in eight (53%). Loss or delay of R2-i/R2c-i was seen in lesions covering the entire trigeminal spinal tract and nucleus (TSTN) at at least one level. These infarctions were located more dorsally within the medulla. Patients with normal blink reflexes showed lesions sparing or involving the TSTN only partially. They more often had incomplete Wallenberg's syndromes and MRI lesions were located more ventrally. CONCLUSIONS: Using digital postprocessing MRI methods it was possible to identify central pathways of late blink reflex in patients with Wallenberg's syndrome. This method is suggested as a new approach to identify incompletely understood functional structures of the brainstem.     

Electrophysiological brain stem investigations in idiopathic narcolepsy

Narcolepsy is associated with various rapid eye movement (REM) sleep abnormalities. Distinct brain stem areas seem to play a prominent role in REM sleep regulation. Recent magnetic resonance imaging (MRI) studies have led to conflicting findings concerning the presence of structural brain stem lesions in patients with idiopathic narcoleptic syndrome. However, multimodal electrophysiological brain stem investigations may reveal functional brain stem abnormalities even in the absence of MRI abnormality. Therefore we investigated brain stem function in 12 idiopathic narcoleptic patients by systematically studying tegmental brain stem pathways. All of the patients met the diagnostic criteria of the International Classification of Sleep Disorders, with typical changes in polysomnography and the multiple sleep latency test. Electrophysiological investigations comprised masseter reflex, blink reflex, masseter inhibitory reflex, early auditory evoked potentials and electrooculography with vestibular testing. In no patient were electrophysiological brain stem abnormalities observed. Our findings do not support the existence of a relevant brain stem lesion in narcoleptic patients with normal neurological status. Received: 23 September 1997 Received in revised form: 23 January 1998 Accepted: 10 February 1998     

Blink reflex in patients with an ischaemic lesion of the brain-stem verified by MRI

The electrically elicited blink reflex was investigated in 25 patients with ischaemic lesions of the pons or the medulla oblongata. Only patients with a lesion on MRI appropriate to the clinical syndrome were included. Twenty patients had an infarction of the pons, bilateral in 5. Additional 5 patients had an infarction of the dorsolateral medulla oblongata. Patients with hemispheric lesions were excluded. Four of the 5 patients with Wallenberg's syndrome showed delayed R2 components to stimulation ipsilateral to the lesion. Additional loss of the ipsilateral R1 component was observed in 1 patient. Fifteen of the 20 patients with pontine infarctions had pathological blink reflexes. All 6 patients with a unilateral pons lesion and an abnormality of R1 had this abnormality on the side contralateral to the lesion. In 3 cases with bilateral pontine infarction R1 was abnormal on one side or on either side. Of 11 patients with a normal R1, 6 had isolated abnormalities of R2 without consistent correlation to the side of the lesion. We conclude that abnormalities of the blink reflex are of minor localizing value in pontine infarction. This may be explained by the fact that a pontine infarction affects either the reflex arch itself or descending pathways that have a modulating influence on the reflex arch. Infarctions of the medulla oblongata, however, have characteristic abnormalities that have already been described.     

The effect of paired stimuli on blink reflex latencies in normal subjects

Introduction: In this study we assessed the effect of paired stimuli on the latencies and amplitudes of the blink reflex. Methods: Blink reflexes were performed with single and paired (5‐ms interstimulus interval) stimuli in 47 patients. The changes in latencies between paired and single stimuli were calculated. Results: Paired stimulation produced two types of R1 waveform morphologies: single‐ and double‐peaked waveforms. Increases in R1 and contralateral R2 latencies with paired stimulation were significantly higher in those with single‐peaked R1 responses compared to those with double‐peaked R1 responses. Conclusions: Interpreting the blink reflex latencies using paired stimulation requires visualization of the R1 waveform morphology. A double‐peaked R1 response requires no change in normal latency values, but the latency of a single‐peaked R1 should be interpreted from the second shock artifact. The effect on the R2 latency is variable. Muscle Nerve, 2011     

Correlation between blink reflex abnormalities and magnetic resonance imaging findings in patients with multiple sclerosis

This study investigates the correlation between brain magnetic resonance imaging findings and blink reflex abnormalities in patients with relapsing remitting multiple sclerosis. Twenty-six patients and 17 healthy subjects were included in this study. Blink reflex test (BRT) results were obtained using right and left stimulations; thus, 52 BRT results were recorded for the patient group, and 34 BRT results were recorded for the control group. The magnetic resonance imaging (MRI) findings were classified based on the existence of brainstem lesions (hyperintense lesion on T2 weighted (W) and fast fluid-attenuated inversion recovery MRI or contrast-enhancing lesion on T1W MRI). Correlation analysis was performed for the BRT and MRI findings. The percentage of individuals with abnormal BRT results (including R1 latency, ipsilateral R2 latency, and contralateral R2 latency) was significantly higher in the patient group as compared to the control group (p values: 0.015, 0.001, and 0.002, respectively). Correlation analysis revealed significant correlations between contralateral R2 latency abnormalities and brainstem lesions (p value: 0.011). Our results showed significant correlation correlations between contralateral R2 latency abnormalities and brainstem lesions and these results may be explained the effects of multiple demyelinating lesions of the brain stem of patients with relapsing remitting multiple sclerosis.     

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.     

电刺激诱发瞬目反射对脑桥梗死患者的预后价值

目的 探讨电刺激诱发瞬目反射(blink reflex,BR)对脑桥梗死患者的预后价值.方法 对43例脑桥梗死患者和37例健康对照组进行电刺激诱发BR的检测,采用欧洲脑卒中评分(The European stroke scale,ESS)和日常生活活动(activity of daily life,ADL)量表对每位患者在BR检查当日和4周末分别进行神经功能缺损程度评分.结果 脑桥梗死组病灶侧R1的潜伏期较对照组明显延长,病灶侧R1的潜伏期较健侧也显著延长(P＜0.001).脑桥梗死组BR各波的异常率以R1最高,占81.4%,而R2和R2′的异常率分别为23.3%和25.6%.R1的异常率显著高于R2和R2′(P＜0.001).双侧脑桥梗死(双侧均有病灶,每侧病灶直径均＞3mm),导致BR各波均未引出.一侧脑桥单个梗死灶,梗死灶直径＞3mm,主要引起R1潜伏期延长;一侧脑桥单个梗死灶,梗死灶直径0.5～3mm,BR各波潜伏期均正常.R1波未引出组神经功能缺损程度最重,ESS评分和ADL评分显著低于R1潜伏期延长组和R1潜伏期正常组(P＜0.001);R1潜伏期正常组预后最好,4周末其ESS评分和ADL评分均较1周内显著提高(P＜0.01和0.001);R1潜伏期延长组次之.结论 脑桥梗死患者的BR异常以R1潜伏期延长为特征.脑桥的病灶主要引起R1异常,进一步提示R1的反射中枢位于脑桥.BR的异常类型可大致反映脑桥梗死病灶的范围,BR的R1异常可作为脑桥梗死患者神经功能缺损程度和预后评价的电生理指标之一.     

Brainstem reflexes and brainstem auditory evoked responses in Huntington''s chorea.

Blink reflex, corneal reflex, jaw reflex, exteroceptive suppression in masseter muscles and brainstem auditory evoked potentials were measured in 20 patients with Huntington's chorea and 12 controls. A significantly increased latency of the second component of the homolateral and heterolateral blink reflex was found in the patient group as compared with the controls. The other investigations revealed no significant differences between patients and controls except for some facilitation of the jaw reflex in the patient group. Increase of second component latency of the blink reflex in the presence of normal corneal reflexes is suggestive of functional impulse conduction disturbance in the lower brainstem. It is discussed whether in Huntington's chorea this is to be attributed to alterations of cortical or striatal influence or to local brainstem abnormalities.     

Brain-stem auditory evoked potentials and blink reflex in friedreich's ataxia

Summary The brain-stem involvement in Friedreich's ataxia (FA) was studied by using brain-stem auditory evoked potentials (BAEPs) and the blink reflex. Ten out of 18 patients had abnormal BAEPs, the main abnormality being complete absence of responses and disappearance of wave V. Combined degeneration of the peripheral and central acoustic pathways probably accounts for these findings. The blink reflex was abnormal in 50% of the cases. The outstanding abnormality was bilateral delay of late responses with normal early response, which could be correlated with the known pallor of the descending trigeminal tracts. In contrast with BAEP findings, blink reflex abnormalities did not correlate with either the age of patients or the severity and duration of the disease. These data suggest a difference in susceptibility to degeneration between the auditory system and neuronal system subserving the blink reflex. We conclude that systematic BAEP and blink reflex recording is useful in the electrophysiological evaluation of FA patients.     

Neurophysiological evaluation of trigeminal and facial nerves in patients with chronic inflammatory demyelinating polyneuropathy

Cranial neuropathy is clinically uncommon in patients with chronic inflammatory demyelinating polyneuropathy (CIDP), but there is little information on the neurophysiological examination of cranial nerve involvement. To determine the incidence of trigeminal and facial nerve involvement in patients with CIDP, the direct response of the orbicularis oculi muscle to percutaneous electric stimulation of the facial nerve and the blink reflex (induced by stimulation of the supraorbital nerve) were examined in 20 CIDP patients. The latency of the direct response was increased in 12 patients (60%) and an abnormal blink reflex was observed in 17 patients (85%). There was no correlation between electrophysiological findings and the latencies of the direct and R1 responses and disease duration or clinical grade in CIDP patients. Nevertheless, the prevalence of subclinical trigeminal and facial neuropathy is extremely high in patients with CIDP when examined by neurophysiological tests.