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.     

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.     

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.     

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.     

A new method to investigate brain stem structural–functional correlations using digital post-processing MRI – reliability in ischemic internuclear ophthalmoplegia

We investigated the reliability of a new digital post-processing magnetic resonance imaging (MRI) technique in ischemic brain stem lesions to identify relations of the lesion to anatomical brain stem structures. The target was a medial longitudinal fasciculus (MLF) lesion, which was evident from ipsilateral internuclear ophthalmoplegia (INO). Sixteen patients with acute unilateral INO and an isolated acute brain stem lesion in T2- and EPI-diffusion weighted MRI within 2 days after the onset of symptoms were studied. The MRI slice direction was parallel and perpendicular to a slice selection of a stereotactic anatomical atlas. The individual slices were normalized and projected in the digitalized atlas. The eye movement disorder was monitored by electro-oculography. In all patients with clinical or subclinical electro-oculographically documented INO and MRI proven brain stem infarction the lesion covered or at least partially overlapped the ipsilateral MLF at one or more atlas levels. We conclude that digital post-processing MRI with normalizing and projecting brain stem lesions in an anatomical atlas is a reliable method to demonstrate the anatomical structures involved by the lesion. Combined with electrophysiological brain stem testing, this method may be a useful tool to identify incompletely understood pathways mediating brain stem reflexes or the generators of evoked potentials.     

Blink reflexes and magnetic resonance imaging in focal unilateral central trigeminal pathway demyelination.

The electrically elicited blink reflex allows quantitative analysis of the corneal reflex which traverses the trigeminal and facial nerves and the brainstem. Two patients presenting with symptomatic unilateral trigeminal lesions are described, in whom the blink reflexes showed conduction block and slowing at predictable sites in the central pathways, and magnetic resonance imaging confirmed precisely the clinical and electrophysiological localisation.     

Hyperekplexia and stiff-man syndrome: abnormal brainstem reflexes suggest a physiological relationship

BACKGROUND AND OBJECTIVES: Hyperekplexia and the stiff-man syndrome (SMS) are both conditions with exaggerated startle suggesting abnormal brainstem function. Investigation of brainstem reflexes may provide insight into disturbed reflex excitation and inhibition underlying these movement disorders. PATIENTS AND METHODS: Using four-channel EMG, we examined four trigeminal brainstem reflexes (monosynaptic masseter, masseter inhibitory, glabella, and orbicularis oculi blink reflexes) and their spread into pericranial muscles in five patients with familial hyperekplexia (FH), two with acquired hyperekplexia (AH), 10 with SMS, and 15 healthy control subjects. RESULTS: Both FH/AH and SMS patients had abnormal propagation of brainstem reflexes into pericranial muscles. All patients with hyperekplexia showed an abnormal short-latency (15-20 ms) reflex in the trapezius muscle with a characteristic clinical appearance ("head retraction jerk") evoked by tactile or electrical stimulation of the trigeminal nerve, but normal monosynaptic masseter reflexes. Inhibitory brainstem reflexes were attenuated in some FH/AH patients. Four of 10 patients with SMS had similar short-latency reflexes in the neck muscles and frequently showed widespread enhancement of other excitatory reflexes, reflex spasms, and attenuation of inhibitory brainstem reflexes. CONCLUSION: Reflex excitation is exaggerated and inhibition is attenuated in both stiff-man syndrome and familial or acquired hyperekplexia, indicating a physiological relationship. Reflex transmission in the brainstem appears biased towards excitation which may imply dysfunction of inhibitory glycinergic or GABAergic interneurons, or both.     

Intraoperative Monitoring and Mapping of the Functional Integrity of the Brainstem

The risk of iatrogenic damage is very high in surgical interventions in or around the brainstem. However, surgical techniques and intraoperative neuromonitoring (ION) have evolved sufficiently to increase the likelihood of successful functional outcomes in many patients. We present a critical review of the methodologies available for intraoperative monitoring and mapping of the brainstem. There are three main groups of techniques that can be used to assess the functional integrity of the brainstem: 1) mapping, which provides rapid anatomical identification of neural structures using electrical stimulation with a hand-held probe, 2) monitoring, which provides real-time information about the functional integrity of the nervous tissue, and 3) techniques involving the examination of brainstem reflexes in the operating room, which allows for the evaluation of the reflex responses that are known to be crucial for most brainstem functions. These include the blink reflex, which is already in use, and other brainstem reflexes that are being explored, such as the masseter H-reflex. This is still under development but is likely to have important functional consequences. Today an abundant armory of ION methods is available for the monitoring and mapping of the functional integrity of the brainstem during surgery. ION methods are essential in surgery either in or around the brainstem; they facilitate the removal of lesions and contribute to notable improvements in the functional outcomes of patients.     

Sensorimotor integration in patients with parkinsonian type multisystem atrophy

Sensorimotor integration is an essential feature of the central nervous system that contributes to the accurate performance of motor tasks. Some patients with multiple system atrophy with parkinsonian features (MSAp) exhibit clinical signs compatible with an abnormal central nervous system excitability to somatosen– sory inputs, such as action myoclonus or enhanced cutaneo–muscular reflexes. To investigate further the site where such dysfunction in sensorimotor integration takes place, we examined the inhibitory effects of a cutaneous afferent volley at two different levels of the motor system in 10 MSAp patients and in 10 agematched healthy volunteers. Electrical digital nerve stimuli were given as the conditioning stimulus for the motor evoked potentials (MEP) elicited by transcranial magnetic stimulation in hand muscles, and for the blink reflex responses obtained in the orbicularis oculi muscles by supraorbital nerve stimulation. Intervals for the conditioning were 20 to 50ms for the MEP and 90 to 110ms for the blink reflex. The MEP was significantly inhibited in test trials in healthy volunteers, reaching a mean of 32% of the baseline values at the ISI of 35 ms. Significant inhibition occurred also in the blink reflex, in which the R2 response was a mean of 12% of baseline values at the ISI of 100 ms. The inhibitory effects were abnormally reduced in 8 patients on the MEP, and in 7 patients on the blink reflex. There were significant group differences between patients and control subjects in the size of the conditioned MEP and blink reflex. These results suggest that sensorimotor integration is abnormal in patients with MSAp in at least two central nervous system sites: the sensorimotor cortex, and the brainstem reticular formation.     

Brainstem dysfunction in variegate porphyria

Introduction: Variegate porphyria (VP) is a rare metabolic disorder that may present as an acute predominantly motor neuropathy. Cranial nerves and brainstem functions have been only scarcely studied. Methods: Brainstem reflexes were examined in symptomatic and non-symptomatic VP mutation carriers of a single family. Results: Similar results were found in the 2 patients with a history of porphyric crises. The blink reflex showed an absence of late responses (R2 and R2c) to stimulation of both sides. The masseter inhibitory reflex showed reduced inhibition of the second phase. The jaw jerk was normal. The asymptomatic carriers did not show any of the abnormalities just noted. Conclusions: Our results are compatible with a central lower pons-upper medulla disorder in the brainstem. We hypothesize that brainstem dysfunction in VP patients with a history of porphyric crises may be due to neurotoxic effects of porphyrin precursors as well as subclinical osmolarity changes due to hyponatremia. Muscle Nerve 46: 426-433, 2012.     

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.     

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.     

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.     

Neurological and pathophysiological analyses of patients with absent auditory brainstem evoked response

Seventeen patients with no auditory brainstem evoked response (ABR) who suffered from various neurological disorders were reported. We evaluated the possibilities of co-existent brainstem lesions in addition to the peripheral impairment in the auditory pathway, by assessing neurological findings and other laboratory examinations, including cranial CT and electrically elicited blink reflex. Patients who showed cranial nerve symptoms other than that of the acoustic nerve or abnormal postural reflexes were suspected to have brainstem dysfunction. It was difficult, however, to exclude the influence from the dysfunction in the more central level CNS. Definite brainstem atrophy was revealed radiologically only in one case who was at the end stage of the degenerative disease. Blink reflex was studied in eleven cases, four of whom revealed abnormal responses, also suggesting brainstem dysfunction. All the five cases, consistent with these abnormal laboratory findings, had shown severe delay in motor development. Other five patients who showed rather good auditory behavior were considered to have 'desynchronization' response to ABR in the auditory pathway at the peripheral level. Many pathophysiological conditions may be involved in the phenomenon of absent ABR, which should be carefully evaluated from the viewpoints of clinical neurology.     

Electrophysiological brainstem testing in the diagnosis of reversible brainstem ischemia

The aim of this study was to evaluate the sensitivity of multimodal electrophysiological brainstem testing in the diagnosis of clinically suspected reversible ischemic deficits of the brainstem compared with diffusion weighted MR imaging. We investigated 158 consecutive patients presenting with signs of acute brainstem dysfunction. Serial electrophysiological brainstem tests including masseter reflex, blink reflex, masseter inhibitory reflex, AEP, MEP, EOG and the oculoauricular phenomenon were applied. In 14 of the 158 patients neurological deficits resolved in less than 24 hours, which was suggestive of a transitory ischemic attack (TIA), 19 patients had brainstem signs for more than 24 hours but less than 1 week, suggestive of a reversible ischemic neurological deficit (RIND). Electrophysiological data indicated acute functional brainstem lesions in 54,5 % of patients with transient clinical brainstem impairment. Lesion detection rate was significantly higher when combining electrophysiological data and MRI (60,4 %) than using acute brainstem abnormalities in diffusion weighted MRI alone (39,4 %). We conclude that diffusion weighted MRI and electrophysiological brainstem testing are complimentary sensitive indicators of acute brainstem lesions in patients with reversible neurological deficits. Correct identification of brainstem ischemia influences the therapeutic regimen and may improve patient outcome. Received: 5 November 2001 Received in revised form: 28 January 2002 Accepted: 1 February 2002     

Perioral reflexes in orofacial dyskinesia and spasmodic dysphonia.

In order to assess the clinical utility of trigemino-facial reflexes in lower facial muscles, we studied perioral reflexes to mechanical and electrical stimulation in 13 patients with spasmodic dysphonia and orofacial dyskinesia and in 7 healthy subjects. Mechanical stimulation of the upper lip of all patients and electrical stimulation of the infraorbital nerve of patients with orofacial dyskinesia elicited larger perioral reflexes than in controls. In the majority of patients, hyperexcitable perioral reflexes were accompanied by increased gain of the blink reflex. In 4 patients, however, trigemino-facial reflexes were enhanced selectively in either the perioral muscles or orbicularis oculi. Our findings suggest that the quantitative assessment of perioral reflexes may provide information about the excitability of brainstem interneurons in cranial dystonia that is complementary to blink reflex studies.     

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.     

Significance of the blink reflex in the Wallenberg syndrome

The blink reflex was studied in 38 cases with lateral medullary lesions (Wallenberg syndrome). Twenty-one blink reflexes were abnormal. The most common abnormality is an afferent delay in the late reflex on the side of the lesion with a normal early reflex. This abnormality is not pathognomonic of the Wallenberg syndrome. The physiopathogeny is discussed.     

Electrophysiological study of the snout reflex in normal subjects and in parkinsonian and pseudobulbar patients

The snout reflex appeared to be electrophysiologically present in a great majority of normal subjects. Nevertheless, a facilitation of the R2 responses of the snout reflex was found in parkinsonian patients while in pseudobulbar patients an augmentation of the R1 took place. The snout reflex, therefore, seemed to behave in a similar way as the blink reflex. In order to explain the reported findings the authors took into account the different effects of the lesions of the lateral and ventral motor system upon the oligo- and multisynaptic reflexes.