Extraocular Motor Nerves Research Articles

Evolution and development of extraocular motor neurons, nerves and muscles in vertebrates

The purpose of this review is to analyze the origin of ocular motor neurons, define the pattern of innervation of nerve fibers that project to the extraocular eye muscles (EOMs), describe congenital disorders that alter the development of ocular motor neurons, and provide an overview of vestibular pathway inputs to ocular motor nuclei. Six eye muscles are innervated by axons of three ocular motor neurons, the oculomotor (CNIII), trochlear (CNIV), and abducens (CNVI) neurons. Ocular motor neurons (CNIII) originate in the midbrain and innervate the ipsilateral orbit, except for the superior rectus and the levator palpebrae, which are contralaterally innervated. Trochlear motor neurons (CNIV) originate at the midbrain-hindbrain junction and innervate the contralateral superior oblique muscle. Abducens motor neurons (CNVI) originate variously in the hindbrain of rhombomeres r4–6 that innervate the posterior (or lateral) rectus muscle and innervate the retractor bulbi. Genes allow a distinction between special somatic (CNIII, IV) and somatic (CNVI) ocular motor neurons. Development of ocular motor neurons and their axonal projections to the EOMs may be derailed by various genetic causes, resulting in the congenital cranial dysinnervation disorders. The ocular motor neurons innervate EOMs while the vestibular nuclei connect with the midbrain-brainstem motor neurons.

External Ocular Movement(EOM)Monitoring

The intraoperative monitoring of extraocular motor nerves allows optimal skull base surgery by protecting the cranial nerves. For detecting cranial nerve function, several methods, such as external ocular movement monitoring with an electrooculogram(EOG), electromyogram(EMG), and piezoelectric device sensors, are present. While being valuable and useful, several problems related to its accurate monitoring persist when scanning from inside the tumor, which might be far from the cranial nerves. Here, we described three modalities, free-run EOG monitoring, trigger EMG monitoring, and piezoelectric sensor monitoring for monitoring external ocular movement. Improvement of these processes is essential for appropriately conducting these procedures during neurosurgical operations without harming the extraocular motor nerves.

Novel method of intraoperative ocular movement monitoring using a piezoelectric device: experimental study of ocular motor nerve activating piezoelectric potentials (OMNAPP) and clinical application for skull base surgeries.

Intraoperative monitoring systems that utilize various evoked potentials for the detection and/or preservation of cranial nerves have become increasingly common due to recent technical and commercial developments, particularly during skull base surgeries. We established a novel system for the intraoperative monitoring of the extraocular motor nerves (eOMNs) using a piezoelectric device capable of detecting imperceptible vibrations induced by ocular movement, with sensors placed on the eyelids alone. We first evaluated the efficacy and reliability of this device for the intraoperative monitoring of eOMNs in two Beagle dogs. Based on the results, we then determined the appropriate stimulation parameters for use in human surgical cases involving removal of various skull base tumors. Animal experiments revealed that a 0.4mA monopolar electrical stimulation was required to elicit significant responses and that these responses were not inferior to those obtained via the electrooculogram/electromyogram. Significant responses were also detected in preliminary clinical investigations in human patients, following both direct and indirect monopolar electrical stimulation of the oculomotor and abducens nerves, although obtaining responses from the trochlear nerve was difficult. Intraoperative monitoring using a piezoelectric device provides a simple and reliable method for detecting eOMNs, especially the oculomotor and abducens nerves. This monitoring system can be adapted to various surgeries for skull base tumor.

O177 Novel method of intraoperative ocular movement monitoring using a piezoelectric device: Experimental study of OMNAPP (ocular motor nerve activating piezoelectric potentials) and clinical application for skull base surgeries

Objectives Intraoperative monitoring for the extraocular motor nerves (eOMNs) using electromyograms are not widely accepted due to their inherent invasiveness. We established a novel system for the intraoperative monitoring of eOMNs using a piezoelectric device capable of detecting imperceptible vibrations induced by ocular movement, with sensors placed on the eyelids alone. Methods We first evaluated the efficacy and reliability of this system for the intraoperative monitoring of eOMNs in two Beagle dogs. The oculomotor nerve of each dog was detected under general anesthesia, following which the detection of ocular movement was evaluated by providing varying levels of stimulation to the nerve. Based on the results of these animal experiments, we then determined the appropriate stimulation parameters for use in some surgical cases of various skull base tumors. Results Animal experiments revealed that 0.4–0.6 mA of monopolar electrical stimulation was required to elicit significant responses, which were not inferior to those obtained via the electrooculogram/electromyogram. Significant responses were also detected in preliminary clinical investigations in human patients following both direct and indirect monopolar electrical stimulation of the oculomotor and abducens nerves, although it was difficult to obtain responses from the trochlear nerve. Conclusions Our findings indicate that intraoperative monitoring system using a piezoelectric device represents a simple and reliable method that can be adapted to various skull base surgeries. Further studies are required to investigate functional outcomes in patientstreated using this intraoperative monitoring system. Significance This intraoperative monitoring system (We call as OMNAPP system) for the eOMNs is useful for skull base surgeries including various transcranial approaches.

Galvanic Vestibular Stimulation: Cellular Substrates and Response Patterns of Neurons in the Vestibulo-Ocular Network.

Galvanic vestibular stimulation (GVS) uses modulated currents to evoke neuronal activity in vestibular endorgans in the absence of head motion. GVS is typically used for a characterization of vestibular pathologies; for studies on the vestibular influence of gaze, posture, and locomotion; and for deciphering the sensory-motor transformation underlying these behaviors. At variance with the widespread use of this method, basic aspects such as the activated cellular substrate at the sensory periphery or the comparability to motion-induced neuronal activity patterns are still disputed. Using semi-intact preparations of Xenopus laevis tadpoles, we determined the cellular substrate and the spatiotemporal specificity of GVS-evoked responses and compared sinusoidal GVS-induced activity patterns with motion-induced responses in all neuronal elements along the vestibulo-ocular pathway. As main result, we found that, despite the pharmacological block of glutamatergic hair cell transmission by combined bath-application of NMDA (7-chloro-kynurenic acid) and AMPA (CNQX) receptor blockers, GVS-induced afferent spike activity persisted. However, the amplitude modulation was reduced by ∼30%, suggesting that both hair cells and vestibular afferent fibers are normally recruited by GVS. Systematic alterations of electrode placement with respect to bilateral semicircular canal pairs or alterations of the bipolar stimulus phase timing yielded unique activity patterns in extraocular motor nerves, compatible with a spatially and temporally specific activation of vestibulo-ocular reflexes in distinct planes. Despite the different GVS electrode placement in semi-intact X. laevis preparations and humans and the more global activation of vestibular endorgans by the latter approach, this method is suitable to imitate head/body motion in both circumstances. Galvanic vestibular stimulation is used frequently in clinical practice to test the functionality of the sense of balance. The outcome of the test that relies on the activation of eye movements by electrical stimulation of vestibular organs in the inner ear helps to dissociate vestibular impairments that cause vertigo and imbalance in patients. This study uses an amphibian model to investigate at the cellular level the underlying mechanism on which this method depends. The outcome of this translational research unequivocally revealed the cellular substrate at the vestibular sensory periphery that is activated by electrical currents, as well as the spatiotemporal specificity of the evoked eye movements, thus facilitating the interpretation of clinical test results.

Intra-operative electrooculographic monitoring to prevent post-operative extraocular motor nerve dysfunction during skull base surgeries.

Background and Aims:Intra-operative identification and preservation of extraocular motor nerves is one of the main goals of surgeries for skull base tumours and this is done by monitoring the extraocular movement (EOM). Intra-operative electromyographic monitoring has been reported, but it is a complex and skilful process. Electrooculography (EOG) is a simple and reliable technique for monitoring EOMs. We aimed to assess the utility of EOG monitoring in preventing extraocular motor nerve dysfunction during skull base surgeries.Methods:In this retrospective cohort study, intra-operative EOG recordings were obtained using disposable needle electrodes placed on the periorbital skin and the polarity of the waves noted for interpretation. Triggered as well as continuous EOG responses were recorded after monopolar electrode stimulation of cranial nerve (CN) during tumour removal which helped the surgeon with careful dissection and avoiding potential nerve injuries.Results:Of the 11 cases monitored, oculomotor and abducent nerves were identified in all cases, but the trochlear nerve could not be definitively identified. Six patients had no pre- or post-operative extraocular motor nerve dysfunction. The other five patients had pre-existing deficits before surgery, which recovered completely in two, significantly in one, and did not improve in two patients at 3–6 months follow-up.Conclusions:EOG was found to be a simple and reliable method of monitoring extraocular motor nerves (CNs III and VI) intraoperatively.

Efficacy of tricaine methanesulfonate (MS-222) as an anesthetic agent for blocking sensory-motor responses in Xenopus laevis tadpoles.

Anesthetics are drugs that reversibly relieve pain, decrease body movements and suppress neuronal activity. Most drugs only cover one of these effects; for instance, analgesics relieve pain but fail to block primary fiber responses to noxious stimuli. Alternately, paralytic drugs block synaptic transmission at neuromuscular junctions, thereby effectively paralyzing skeletal muscles. Thus, both analgesics and paralytics each accomplish one effect, but fail to singularly account for all three. Tricaine methanesulfonate (MS-222) is structurally similar to benzocaine, a typical anesthetic for anamniote vertebrates, but contains a sulfate moiety rendering this drug more hydrophilic. MS-222 is used as anesthetic in poikilothermic animals such as fish and amphibians. However, it is often argued that MS-222 is only a hypnotic drug and its ability to block neural activity has been questioned. This prompted us to evaluate the potency and dynamics of MS-222-induced effects on neuronal firing of sensory and motor nerves alongside a defined motor behavior in semi-intact in vitro preparations of Xenopus laevis tadpoles. Electrophysiological recordings of extraocular motor discharge and both spontaneous and evoked mechanosensory nerve activity were measured before, during and after administration of MS-222, then compared to benzocaine and a known paralytic, pancuronium. Both MS-222 and benzocaine, but not pancuronium caused a dose-dependent, reversible blockade of extraocular motor and sensory nerve activity. These results indicate that MS-222 as benzocaine blocks the activity of both sensory and motor nerves compatible with the mechanistic action of effective anesthetics, indicating that both caine-derivates are effective as single-drug anesthetics for surgical interventions in anamniotes.

A novel simple real-time electrooculographic monitoring system during transsphenoidal surgeries to prevent postoperative extraocular motor nerve dysfunction

In transsphenoidal surgery (TSS) for pituitary tumors, the use of endoscopes allows approach to the lateral sides in and around the cavernous sinus. However, this approach is often associated with a risk of cranial nerve dysfunction causing impaired extraocular movement. We employed a novel, simple, and real-time monitoring system using electrooculography during TSS to avoid postoperative extraocular motor nerve dysfunction. A conventional electroencephalograph, which is available in every hospital, was used to detect effects induced by intraoperative manipulation on the cranial nerves related to extraocular movement (EOM) during TSS for pituitary adenomas. One hundred patients with pituitary adenomas who underwent endonasal endoscope-assisted TSS with EOM monitoring were included in the present study. When the extraocular motor nerves were stimulated mechanically directly or even indirectly by surgical procedures, abnormal extraocular muscle responses [electrooculograms (EOGm)] appeared on the monitor screen. When repeated or continuous EOGm were recorded, surgical procedures were discontinued briefly for around 5 to 10s. The EOGm disappeared promptly when surgical procedures were stopped. Permanent extraocular dysfunction did not occur in the present series of patients. One, who was the fifth patient in the present series, of 100 patients (1.0%) had transient delayed diplopia after TSS. We have not experienced any more postoperative EOM dysfunction since the first case. EOM monitoring during TSS is a novel, efficient, and simple method to prevent postoperative cranial nerve palsy related to EOM.

Peripheral Neuropathy and VIth Nerve Palsy Related to Randall Disease Successfully Treated by High-Dose Melphalan, Autologous Blood Stem Cell Transplantation, and VIth Nerve Decompression Surgery

Randall disease is an unusual cause of extraocular motor nerve (VI) palsy. A 35-year-old woman was hospitalized for sicca syndrome. The physical examination showed general weakness, weight loss, diplopia related to a left VIth nerve palsy, hypertrophy of the submandibular salivary glands, and peripheral neuropathy. The biological screening revealed renal insufficiency, serum monoclonal kappa light chain immunoglobulin, urinary monoclonal kappa light chain immunoglobulin, albuminuria, and Bence-Jones proteinuria. Bone marrow biopsy revealed medullar plasma cell infiltration. Immunofixation associated with electron microscopy analysis of the salivary glands showed deposits of kappa light chains. Randall disease was diagnosed. The patient received high-dose melphalan followed by autostem cell transplantation which led to rapid remission. Indeed, at the 2-month followup assessment, the submandibular salivary gland hypertrophy and renal insufficiency had disappeared, and the peripheral neuropathy, proteinuria, and serum monoclonal light chain had decreased significantly. The persistent diplopia was treated with nerve decompression surgery of the left extraocular motor nerve. Cranial nerve complications of Randall disease deserve to be recognized.

Human Orbital Sympathetic Nerve Pathways

To determine pathways of sympathetic nerves from the orbital apex to the eyelids in human cadaver tissue using immunohistochemistry. Human cadaver orbit tissue was sectioned and immunolabeled with a monoclonal antityrosine hydroxylase antibody. In the orbital apex, the nasociliary, frontal, lacrimal, and maxillary branches of the trigeminal nerve demonstrated intense staining upon entering the orbit. Immunoreactive axons from the nasociliary and frontal nerves were observed to join the extraocular motor nerves in the posterior orbit. A plexus of immunolabeled nerves was observed to accompany the ophthalmic artery as it entered the orbital apex. The ophthalmic artery and its branches throughout the orbit demonstrated staining of nerve fibers in the peripheral muscularis. The nasociliary nerve contributed sympathetic branches to the ciliary ganglion. Nerves passing through the ciliary ganglion and a few ganglion cell bodies demonstrated mild to moderate tyrosine hydroxylase reactivity. Axons within the short and long ciliary nerves demonstrated strong tyrosine hydroxylase reactivity and were observed to enter the posterior sclera and the suprachoroidal space. The lacrimal gland demonstrated mild pericapillary staining and occasional stromal nerve fibers reactive to the antityrosine hydroxylase antibody. Müller muscle and the inferior tarsal muscle possessed a strong tyrosine hydroxylase-reactive nerve supply that appeared to originate from the anterior terminal branches of the nasociliary and lacrimal nerves. Sympathetic nerves enter the orbit via the first and second divisions of the trigeminal nerve and a plexus of nerves surrounding the ophthalmic artery. Extraocular motor nerves receive a sympathetic nerve supply from the sensory nerves in the posterior orbit. Some ciliary ganglion cell bodies demonstrated tyrosine hydroxylase-like reactivity, suggesting a sympathetic modulatory role for the ciliary ganglion. Sympathetics innervate ocular structures via the posterior ciliary nerves. Sympathetic axons travel anteriorly in the orbit via the nasociliary and lacrimal nerves to innervate the sympathetic eyelid muscles. Sympathetic nerves also travel with the frontal branch of the ophthalmic nerve to innervate the forehead skin. The ophthalmic artery and all of its branches contain a perivascular sympathetic nerve supply that may be involved in regulation of blood flow to ocular and orbital structures.

Intra-Operative electromyographic monitoring of extra-ocular motor nerves (Nn. III, VI) in skull base surgery.

Extraocular motor nerves (Nn. III, IV, VI) are at risk of damage during skull base surgery. A new recording technique was employed in 18 patients suffering from various skull base tumours in order to extend intra-operative EMG monitoring to the extra-ocular muscles. Selective intra-operative EMG recordings were obtained from extra-ocular muscles by placement of single-shafted bipolar needle electrodes under the guidance of B-mode ultrasound to visualise the needle tip within the target muscle in the orbital cavity. Following bipolar electrical stimulation, the oculomotor nerve (N.III) was intra-operatively identified in 5 out of 7 cases, and the abducens nerve (N.VI) in 12 out of 18 cases. Postoperative (3-6 months) oculomotor nerve function remained unchanged in 5 and improved in 2 patients. No permanent deterioration was observed. Abducens nerve function deteriorated in two patients and improved in one case, but remained unchanged in 15 cases. No side effects occurred. There was neither any distinct relation of ocular motor nerve function to the kind and extent of SMA ("spontaneous muscle activity") patterns, nor could such relationship be detected with concern to neurophysiological parameters (latencies, amplitudes) of electrically evoked CMAP ("compound muscle action potentials"). The EMG technique proposed proved to be mainly effective as a mapping tool for intra-operative localisation and identification of ocular motor nerves in skull base surgery. However, the predictive value of conventional neurophysiological parameters for clinical outcome, seems to be rather poor. Further studies on a larger number of patients are therefore required to develop new quantification techniques which enable an intra-operative prediction of ocular motor nerve deficits. Further efforts are also necessary to extend this technique to the trochlear nerve.

Guillain-Barré syndrome in Taiwan: a clinical study of 167 patients

OBJECTIVETo identify clinical characteristics of various forms of Guillain-Barré syndrome in Taiwan.METHODSThe clinical and electrophysiological data of 167 consecutive patients with Guillain-Barré syndrome admitted to Chang Gung Memorial Hospital, a...

The organization of the electromotor nucleus and extraocular motor nuclei in the stargazer (Astroscopus y-graecum).

The organization of the oculomotor and electromotor systems was examined in the stargazer, a teleost. The electromotor system in these animals is a derivative of the oculomotor system. The extraocular motor nuclei and nerves consist of approximately equal numbers of motoneurons and axons (about 100 per muscle). In contrast, electromotor axons appear to branch several times within the intracranial portion of the IIIrd nerve. The topographical organization of the motoneurons was examined using retrograde transport of horseradish peroxidase injected into the electric organ or eye muscles. Electromotor and oculomotor neurons form distinct populations. Each electric organ receives a strong ipsilateral and a weak contralateral innervation. Individual eye muscles receive unilateral innervations with the expected laterality. Within the oculomotor nucleus there is some topographical separation of motoneurons innervating each muscle. Antidromic field potentials confirm the identity of the electromotor nucleus.

Tuberculoma of the left optic nerve and chiasm.

TUBERCULOMA of the central nervous system (CNS) is rare in nations with a high standard of living. In other countries such as India, however, the incidence of tuberculoma among intracranial tumors even in recent years has been as high as 20%.¹ A high incidence of ophthalmologic abnormalities occurs in patients with intracranial tuberculomas, even though the lesions do not directly involve the central visual pathways. The most common abnormalities are extraocular motor nerve palsies, visual field defects, and impaired visual acuity, all of which are usually secondary to increased intracranial pressure. A review of the literature indicates that it is rare for tuberculomas to involve directly the central visual pathways. In 1862, Cruveilhier²described the first case of tuberculoma involving an optic nerve, and five years later Hjort³reported the first case of chiasmal involvement. Since then, only 11 cases of tuberculoma directly involving either the chiasm

Extraocular motor disturbances in primary brain tumors.

The incidence of disorders of involvement of the third, sixth, and fourth cranial nerves in a group of 235 primary brain tumor cases, verified by autopsy, admitted to the Philadelphia General Hospital over a 20-year period was studied. No cases of metastatic tumors, tumors by extension, granulomas, vascular malformations, or subclinical tumors, and no cases admitted within 12 hours of death were included in this survey. There were 157 gliomas, of which over 50% were glioblastoma multiforme. The remaining, nongliogenous group comprised 78 tumors, of which over 60% were meningiomas. Sixty cases showed extraocular motor involvement, most frequently encountered (50% of cases) as unilateral isolated third nerve palsy. Abducens involvement was half as frequent and was also usually unilateral and isolated. No instance of isolated trochlear palsy was reported. Combinations of extraocular motor nerve involvement, more frequently bilateral, occurred in 20% of cases. The brain tumor cases were divided into