The corneal reflex is an involuntary blinking of the eyelids, normally within 0.1 s, in response to the stimulation of the cornea. In conscious healthy subjects, stimulation should elicit both a direct and consensual response (blinking of the opposite eye). BR, as a relatively novel entity of IONM, is considered the electronic equivalent of this reflex.

Eric Kugelberg first described this reflex in humans in 1952 (4). The reflex and its pathway were described in detail by Jun Kimura in 2001 in conscious subjects (5). Vedran Deletis first reported how to record BR intra-operatively under general anaesthesia using propofol in 2009 with a successful rate of 86.2% (6). When the cornea is touched, an afferent impulse from either free nerve endings or mechanoreceptors within the corneal epithelium is sent by way of nasociliary nerve and its long ciliary nerve branches of the ophthalmic division of the trigeminal nerve (CN V) to the principal sensory nucleus (aka chief sensory nucleus) of CN V that is located in the rostral pons. Axons then project bilaterally to facial motor nucleus, which initiating the efferent motor response via the temporal and zygomatic branches of the facial nerve (CN VII), leading to the contraction of orbicularis oculi muscles and coordinated eye closure (blink). The rate of blinking is modulated by the blinking centre at the globus pallidus of the basal ganglia (7).

There are two stages to this reflex (8). Large-diameter myelinated A-beta fibers activate the initial movement of the eyelid on the ipsilateral side and provide the early response. Other smaller fiber types activate the late-stage reflex, which stimulates facial nerves bilaterally so that both eyes blink. Inputs from the secondary motor system (e.g., interpositus nucleus of the cerebellum, red nucleus, and reticular activating system) can also modulate this late-stage reflex (9).

Reduced corneal reflex and blinking can occur in various physiological and pathological conditions like old age, pregnancy (10), glaucoma, diabetes, herpetic keratitis, progressive supranuclear palsy, and Parkinson's disease (11, 12). Loss of sensory innervation of the cornea can result in a vision-threatening clinical condition known as neurotrophic keratopathy, which is characterized by reduced corneal sensation, tear film abnormalities and, in the most severe cases, persistent corneal epithelial defects, ulceration, and perforation of the stroma (12).

A stable R1 response is elicited using a train-of-four constant-current stimuli with an inter-stimulus interval of 2 ms, 300 μs pulse width and intensity of up to 40 mA at our hospital. Recording parameters are a time sweep of 50 ms and an amplification of 25–50 μV with a bandpass of 10–3 k Hz. The intensity required for optimal R1 response is found to be quite variable among individual patients due to inter-personal variability of response to anaesthesia as well as brain pathologies. In principle, the intensity of stimulation can be increased until there is a movement artefact in the EMG of contralateral orbicularis oculi or ipsilateral orbicularis oris. By convention, it is common to define an amplitude drop by half or more of a wave from the baseline as a significant change in IONM and thus we arbitrarily adopt it as our definition in the beginning. R1 signal loss or amplitude drop by half or more from the baseline is regarded as a significant change in BR response.

The BR can be monitored very frequently, as shown in the waterfall diagram in Figure 2. Stable BR tracings as the baseline are acquired before the opening of the skull bone. BR is recorded again as another reference after the opening of dura when there will be loss of cerebrospinal fluid and exposure of the brain to the cooler atmospheric air. It is well known that most IONM waveforms are temperature sensitive. At this point, the temperature of the operating field may gradually fall from normal core body temperature to room temperature unless warm normal saline irrigation is administered frequently. Then, during the micro-dissection, nonstop BR monitoring is performed, and it can be acquired as frequent as every minute. Finally, upon the closure of dura, the last BR will be recorded.

In this study, standardized clinical assessment of corneal reflex and sensation is performed. The patient is approached from the side, out of the line of vision to avoid eliciting a menace response. The cornea is lightly touched with a thin strand of clean cotton. Blinking and tearing in that eye (direct corneal reflex) are observed as well as blinking over the other eye (consensual corneal reflex). The patient is asked to compare the sensation of touch over the cornea bilaterally. It is classified as a decreased response if there is a delay in blink or decreased sensation of touch over the cornea.

In addition, the facial nerve function is assessed according to the House-Brackmann grading system, pre-operatively, as well as on day one and at third month post-operatively. During the follow-up, the patients are assessed by clinicians who have access to the imaging and operation records. However, they do not know about the exact intra-operative BR findings that are archived by the IONM nurses during the operation. Pre-operative tumour volume is determined by volumetric measurement in a neuronavigation planning software with the tumour contouring done by the neurosurgeon. The maximal midline shift (MLS) of the brainstem is measured, using readily identifiable anatomical landmarks, namely cerebral aqueduct, mid-point of interpeduncular fossa, and median sulcus of the fourth ventricle in the T2-weighted images (T2WI) of the MRI (Figure 3). Patients' intra-operative findings and post-operative clinical outcomes are correlated and reported. Data are analysed using IBM SPSS Statistics version 29.0 using non-parametric tests with statistical significance set at p < 0.05.

In the 30 patients with successful BR IONM, their BR is decreased significantly (four patients; 13.3%) or lost (two patients; 6.7%) in a total of six patients (20%) at the end of operation. For all patients with transient drop in R1 during the surgery, there are no new deficits if the R1 recovered at the end of operation. There is one (patient 11) with diminished but not reaching 50% amplitude drop in R1 and the patient does not have post-operative corneal sensation problem or ulceration. For the four patients (13.3%) with significant decrease in BR response, all have decreased ipsilateral corneal sensation and one has transient ulceration and keratopathy post-operatively, while for the two patients (6.7%) with BR lost, all have corneal ulcerations and exposure keratitis documented and managed by ophthalmologists. Considering all significant changes in BR and all post-operative corneal complications as post-operative neurological deficits, the statistic parameters of using BR response in detection of deficits are listed in Table 1 as follows.

For the stimulation parameters and recording techniques, there are slight variations in the literature, which are summarized in Table 2. Although TIVA is routinely used in IONM, there can be occasions that it is necessary to change the rate of infusion of anaesthetic agents. We use a train-of-four stimuli to overcome the inhibitory effect of the inadvertent fluctuation of anaesthetic drugs to ensure having a satisfactory R1 waveform in BR monitoring. The use of the train in stimulation is also reported by the Turkey (16) and Beijing (3) groups. We do not use halogenated agents, as in the Beijing (3) group, lest they can affect the other modalities of IONM.

We use surface electrodes over supraorbital nerves for more reliable stimulation, and this is similar to using surface electrodes for median nerve stimulation in SSEP. We find that subdermal needle electrodes can sometimes be far away from the nerve or inadvertently puncture and damage the nerve. The presence of control electrodes can detect and avoid inadvertent current spread that leads to false-positive signals that could be mistakenly recorded as genuine R1. This borrows the concept of detecting after-discharges in direct cortical stimulation in awake craniotomy that helps to determine the maximal safe and effective stimulation.

We use the criteria of R1 wave amplitude decrease by 50% or more, or total loss of R1 wave as the criteria for significant change in BR IONM. This supports the criteria that were used by the Turkey (16) and Beijing (3) groups and has comparable satisfactory overall accuracies.

In one patient (No.26), there is no MLS despite the volume of the tumour being 3.2 cm³. This can sometimes happen when the tumour is mainly over the cistern and/or cerebellar region and not causing any shift in the brainstem. For example, for Koos grade I to III vestibular schwannoma, there will not be a significant shift in the brainstem in the pre-operative MRI. If, during excision of the tumour, using appropriate dynamic retraction after CSF is duly released from the cistern, it is possible to remove the tumour without causing a significant shift in the brainstem. Therefore, it is important to consider the parameter of maximal MLS in addition to the tumour volume when using BR IONM.

Studies postulated that BR can predict post-operative facial palsy even better than facial corticobulbar MEP (FCoMEP) (13, 14). In our two patients (patients 8 and 15) with complete BR loss but intact FCoMEP, although they have corneal sensation disturbances and ulcerations, they do not have post-operative facial palsy. Both patients are managed early by ophthalmologists within post-operative two days and have a satisfactory outcome. We believe that BR may have a role that is more than another supplementary monitoring of facial nerve function as its neural pathway included both trigeminal and facial nerves pathways and R1 in BR is mainly related to the trigeminal pathway.

In addition, FCoMEP may cause extraneous movement interfering the microsurgery (3). This extraneous movement can also create false-positive recordings in intra-operative FCoMEP and BR monitoring, due to the vicinity of the facial muscles. In our study, we utilize the As Low As Reasonably Practicable principle in all our intra-operative stimulation, and in our experience, the pick-up rate of extraneous orbicularis oculi responses by FCoMEP is two out of 30 patients (6.7%). These are cases (case 11 and case 23 in Table 3) that increasing stimulation by no more than 20% from baseline was given for recording when the FCoMEPs show a reduction in amplitude. Furthermore, in our study, we stimulate the ipsilateral supraorbital nerve while using a pair of control electrodes placed in the midline to detect and avoid unwanted movement artefacts. As a result, there is no interference with microsurgery at all when utilizing BR.

With regard to the impact on management, for patients with significant change in BR, we suggest early involvement of ophthalmologists and meticulous preventive eye care measures such as temporary tarsorrhaphy to avoid undesirable complications like exposure keratitis, ulceration, blindness, and other visual disturbances.

The current study presents a prospective cohort of 42 consecutive patients with posterior skull base neurosurgery using frequent BR IONM for monitoring of the corneal reflex and sensation under general anaesthesia. Given the variability in patient outcomes and the complexity of skull surgeries, this relatively small sample size may limit the study's statistical power to detect significant associations or draw definitive conclusions. Nevertheless, we reported statistically significant findings as well as the diagnostic accuracy of BR using our described method of electrode placement, stimulation and recording parameters, and diagnostic criteria. We hope that our report of the novel use of this technique may arouse the interest of the skull base neurosurgery community and possibly lead to further verification of our findings in a larger cohort.