Smoothened overexpression causes trochlear motoneurons to reroute and innervate ipsilateral eyes.

The trochlear projection is unique among the cranial nerves in that it exits the midbrain dorsally to innervate the contralateral superior oblique muscle in all vertebrates. Trochlear as well as oculomotor motoneurons uniquely depend upon Phox2a and Wnt1, both of which are downstream of Lmx1b, though why trochlear motoneurons display such unusual projections is not fully known. We used Pax2-cre to drive expression of ectopically activated Smoothened (SmoM2) dorsally in the midbrain and anterior hindbrain. We documented the expansion of oculomotor and trochlear motoneurons using Phox2a as a specific marker at E9.5. We show that the initial expansion follows a demise of these neurons by E14.5. Furthermore, SmoM2 expression leads to a ventral exit and ipsilateral projection of trochlear motoneurons. We compare that data with Unc5c mutants that shows a variable ipsilateral number of trochlear fibers that exit dorsal. Our data suggest that Shh signaling is involved in trochlear motoneuron projections and that the deflected trochlear projections after SmoM2 expression is likely due to the dorsal expression of Gli1, which impedes the normal dorsal trajectory of these neurons.

Electrophysiology of Extraocular Cranial Nerves: Oculomotor, Trochlear, and Abducens Nerve.

The utility of extraocular cranial nerve electrophysiologic recordings lies primarily in the operating room during skull base surgeries. Surgical manipulation during skull base surgeries poses a risk of injury to multiple cranial nerves, including those innervating extraocular muscles. Because tumors distort normal anatomic relationships, it becomes particularly challenging to identify cranial nerve structures. Studies have reported the benefits of using intraoperative spontaneous electromyographic recordings and compound muscle action potentials evoked by electrical stimulation in preventing postoperative neurologic deficits. Apart from surgical applications, electromyography of extraocular muscles has also been used to guide botulinum toxin injections in patients with strabismus and as an adjuvant diagnostic test in myasthenia gravis. In this article, we briefly review the rationale, current available techniques to monitor extraocular cranial nerves, technical difficulties, clinical and surgical applications, as well as future directions for research.

Strabismus.

Defining the type of strabismus creates a framework for work-up and management. Comitant esotropia is most commonly a childhood condition treated with glasses and surgery. Comitant exotropia is often a childhood condition that may require surgical correction. Microvascular disease is the most common cause of ocular cranial nerve palsies in adult patients.

Skew deviation e ocular tilt reaction versus paralisia do nervo troclear / Skew deviation and ocular tilt reaction versus trochlear nerve palsy

Skew deviation é o desalinhamento vertical dos olhos causado por disfunção unilateral no tronco cerebral, cerebelo ou sistema vestibular periférico, comprometendo as vias por onde transitam impulsos dos órgãos otolíticos aos núcleos oculomotores. Está frequentemente associado a torção ocular e inclinação da cabeça, compondo, assim, a ocular tilt reaction. Neste artigo os autores ressaltam aspectos históricos, fisiológicos, etiopatogênicos e clínicos que contribuem para caracterizar ambas as condições, além da diferenciação clínica com a paralisia do nervo troclear.

Skew deviation is the vertical misalignment of the eyes caused by unilateral dysfunction in the brain stem, cerebellum or peripheral vestibular system, resulting imbalance in otolith input to the oculo-motor system. It's often associated with ocular torsion and head tilt, which together comprise the ocular tilt reaction. In this article the authors emphasize the historical, physiological, etiopathogenesis and clinical aspects that contribute to characterize both conditions, and help to differentiate them clinically from trochlear nerve palsy.

Supraorbital and supratrochlear stimulation for trigeminal autonomic cephalalgias.

Trigeminal autonomic cephalalgias (TAC) is a rare primary headache disorder with challenging and limited treatment options for those unfortunate patients with severe and refractory pain. This article will review the conventional pharmacologic treatments as well as the new neuromodulation techniques designed to offer alternative and less invasive treatments. These techniques have evolved from the treatment of migraine headache, a much more common headache syndrome, and expanded towards application in patients with TAC. Specifically, the article will discuss the targeting of the supratrochlear and supraorbital nerves, both terminal branches of the trigeminal nerve.

Congenital trochlear-oculomotor synkinesis.

Synkinesis of the extraocular muscles forms a subset of congenital ocular motility abnormalities termed congenital cranial dysinnervation disorders. Synkinesis most frequently involves the abducens or oculomotor nerves and rarely the trochlear nerve. Only 3 such patients have been described in the literature. We report an isolated case of trochlear-oculomotor synkinesis in a healthy 6-year-old boy and discuss the proposed pathophysiology of this disorder.

Sihler staining study of anastomosis between the facial and trigeminal nerves in the ocular area and its clinical implications.

INTRODUCTION: The trigeminal nerve (CN V) supplies mostly sensory innervation to the face, and the facial nerve (CN VII) conveys primarily motor fibers. The aim of this study was to elucidate their distributions and anastomoses. METHODS: Fourteen specimens of hemisectioned faces were gathered from human cadavers and stained with Sihler staining. RESULTS: The temporal (Tbr), zygomatic (Zbr), and buccal (Bbr) branches of CN VII formed trigeminofacial anastomoses in the ocular area. Communications were observed between the supraorbital nerve and the Tbr (85.7%), the infraorbital nerve and the Bbr (100%) and Zbr (28.6%), and the zygomaticofacial nerve and the Zbr (41.7%). Anastomoses were formed between the supratrochlear nerve and the Tbr (57.1%) and Bbr (50%), and the infratrochlear nerve and the Bbr (85.7%). CONCLUSIONS: Motor and sensory axons to the face contribute to trigeminofacial anastomoses, which may play key roles in subtle movements of muscles of facial expression.

Infranuclear ocular motor disorders.

This chapter covers the very large number of possible disorders that can affect the three ocular motor nerves, the neuromuscular junction, or the extraocular muscles. Conditions affecting the nerves are discussed under two major headings: those in which the site of damage can be anatomically localized (e.g., fascicular lesions and lesions occurring in the subarachnoid space, the cavernous sinus, the superior orbital fissure, or the orbit) and those in which the site of the lesion is either nonspecific or variable (e.g., vascular lesions, tumors, "ophthalmoplegic migraine," and congenital disorders). Specific comments on the diagnosis and management of disorders of each of the three nerves follow. Ocular motor synkineses (including Duane's retraction syndrome and aberrant regeneration) and disorders resulting in paroxysms of excess activity (e.g., neuromyotonia) are then covered, followed by myasthenia gravis and other disorders that affect the neuromuscular junction. A final section discusses disorders of the extraocular muscles themselves, including thyroid disease, orbital myositis, mitochondrial disease, and the muscular dystrophies.

[Intraoperative identification of oculomotor, trochlear and abducent nerves in surgery of invasive cranioorbital tumors (new technique)].

BACKGROUND: Aim of the study was to evaluate effectiveness of intraoperative identification of oculomotor nerves (OMN) in resection of skull base tumors invading superior orbital fissure and cavernous sinus. MATERIALS AND METHODS: 69 patients with cranioorbital tumors operated in Burdenko Neurosurgical Institute (Moscow, Russia) since 2000 until 2005 were included in the study. They were divided into 2 groups: 19 patients treated with intraoperative identification of OMN and 50 patients in the control group. Craniorbital meningiomas were in the majority among all cases. Intraoperative identification of OMN was performed using coaxial electrode while muscular response was registered through electrodes inserted in m. levator palpebrae superioris, m. obliquus superior and m. rectus lateralis (for III, IV and VI cranial nerves, respectively). Identification of IMN trunci was repeated throughout the whole stage of tumor resection for their preservation. RESULTS: comparison of dynamics of oculomotor dysfunction in early postoperative period in patients of both groups demonstrated that intraoperative identification of OMN allowed to decrease the frequency of oculomotor deficit. The rates in main and control groups were: for III and IV nerves--37% and 68% (p < 0.05), for VI nerve--47% and 54% (p > 0.05), respectively. CONCLUSION: application of intraoperative identification of OMN allows to decrease the risk of oculomotor deterioration due to III and IV nerve dysfunction by 1.8 times. Technically the method is quite simple and not time-consuming procedure.

Ophthalmoplegia with migraine in adults: is it ophthalmoplegic migraine?

OBJECTIVE: Ophthalmoplegic migraine (OM) is a rare disorder characterized by recurrent oculomotor nerve palsy in children, following migraine headaches. We report 62 adults, seen consecutively, who developed acute ophthalmoplegia with severe attacks of migraine over a 10-year (1996-2005) period. An overwhelming majority of these patients had an antecedent worsening in severity of migraine headaches, before the ophthalmoplegic attack. METHODS: Sixty-two patients, aged 15-68 years, with an acute attack of OM underwent detailed clinical, biochemical, and neuroradiological evaluation. RESULTS: There were 62 patients with 86 attacks of OM. Whereas 48 patients had a single attack, 14 had 2 or more attacks, fulfilling the International Headache Society criteria for probable and definite OM, respectively. At presentation, isolated abducens, oculomotor, and trochlear nerve involvements were seen in 35 (56.5%), 21 (33.9%), and 5 (8.1%) patients, respectively. One patient had simultaneous involvement of 3rd and 6th nerves. Fifty-one (82.3%) patients exhibited an antecedent worsening in severity of migraine, before developing ophthalmoplegia during (59/95.2%) or within 24 hours (3/4.8%) of a severe migraine attack, respectively. Detailed biochemistry and cranial neuroimaging were normal. No case had any nerve enhancement. Use of steroids hastened recovery (P < .05). CONCLUSION: We conclude: (1) OM in adults is characterized by single attacks of ophthalmoplegia in a great majority of patients; and (2) 6th nerve involvement occurs commonly. Our results indicate that moving OM to the chapter on cranial neuralgias in the second edition of the International Headache Classification may be premature, since nerve palsy occurred during a severe migraine attack in all patients.

Isolated palsies of cranial nerves III, IV, and VI.

In this article, isolated palsies of cranial nerves III, IV, and VI are addressed. After discussion of the pertinent clinical anatomy of cranial nerves III, IV, and VI, the isolated involvement of each of these oculomotor nerves is defined. Based on a review of the literature, methods of evaluation and follow-up of patients presenting with diplopia from lesions of these cranial nerves are presented.

Ophthalmoplegic migraine in a 15-year-old Ethiopian: case report and literature review.

The International Headache Society (IHS) defines ophthalmoplegic migraine (OM) as recurrent attacks of headache with migrainous characteristics, associated with paresis of one or more ocular cranial nerves (commonly the third cranial nerve), and in the absence of any demonstrable intracranial lesion other than MRI changes within the affected nerve. According to the IHS criteria, it is diagnosed when at least two attacks with migraine-like headaches are accompanied with, or followed within 4 days of onset by, paresis of one or more of the third, fourth or sixth cranial nerves. Parasellar, orbital fissure and posterior fossa lesions should be ruled out by appropriate investigations. It is unlikely that OM is a variant of migraine, since the headache often lasts for a week or more and there is a latent period of up to 4 days from the onset of headache to the onset of ophthalmoplegia. Furthermore, in some cases MRI shows gadolinium uptake in the cisternal part of the affected cranial nerve and this suggests that the condition may be a recurrent demyelinating neuropathy. In general, patients demonstrated a: (1) prolonged time for symptom resolution to occur (median time 3 weeks); (2) tendency for recurrent episodes to have more severe and persistent nerve involvement; (3) evidence of permanent neurological sequelae with recurrent episodes (30% of patients); (4) rapid improvement and shortened duration with corticosteroid therapy and; (5) transient, reversible MRI contrast enhancement of the affected cranial nerve (86% of patients). Different pathogenetic mechanisms, which include compressive, ischemic and inflammatory, have been suggested for OM. Here, a 15-year-old Ethiopian with recurrent attacks of headache and third nerve palsy is presented. The subsequent discussion focuses on current evidences with regard to the clinical characteristics, possible pathogenetic mechanisms and treatment. Finally, a brief discussion of the situation in Africa will be presented.

Upbeat nystagmus from a demyelinating lesion in the caudal pons.

A 51-year-old man developed positional vertigo, ataxia, dysgeusia, diplopia, and oscillopsia. Eye movement examination and video-oculographic recording disclosed primary position upbeat nystagmus (PPUN) and a right internuclear ophthalmoplegia. Brain MRI showed a small focal lesion in the right dorsal tegmentum of the caudal pons with signal characteristics consistent with a primary demyelinating central nervous system disease. PPUN has not been described previously with a lesion in such a location. Clinicoanatomic correlation in this patient suggests that a lesion of the superior vestibular nucleus and its efferent crossing ventral tegmental tract could be responsible for the PPUN. This case report contributes to a better understanding of the role of this pathway in humans.

The effect of acute superior oblique palsy on vertical pursuit in monkeys.

PURPOSE: To investigate vertical smooth pursuit eye movements in monkeys with acute acquired superior oblique palsy (SOP). METHODS: The trochlear nerve was severed intracranially in two rhesus monkeys. After surgery, the paretic eye was patched for 6 or 9 days, and then binocular viewing was allowed. Eye movements were measured with binocular, dual search coils, before and after surgery, under monocular viewing conditions. Vertical pursuit movements along the midline were elicited by using triangular-wave (20 deg/s, +/-20 degrees ) or step-ramp (20 deg/s) stimuli at a distance of 66 cm. RESULTS: During the early post-lesion period, before binocular viewing was allowed, pursuit velocity of the paretic eye during triangular-wave tracking was lower than that of the normal eye. When the viewing eye crossed straight ahead, the changes in pursuit velocity conjugacy were similar for upward and downward tracking. After habitual binocular viewing was allowed, differences between upward and downward pursuit emerged. When measured approximately 30 days after lesioning, this directional asymmetry was less during the open-loop period of step-ramp tracking than during triangular-wave tracking. CONCLUSIONS: Rhesus monkeys with acute acquired SOP show characteristic changes in vertical pursuit, with deficits for both upward and downward tracking, and differences between the initiation of step-ramp pursuit and the sustained response during triangular-wave tracking. The habitual viewing condition (monocular versus binocular) also affected the pattern of deficit.

The role of intraoperative monitoring of oculomotor and trochlear nuclei -safe entry zone to tegmental lesions.

OBJECTIVE: A safe entry zone to tegmental lesions was identified based on intraoperative electrophysiological findings, the compound muscle action potentials (CMAP) from the extraocular muscles, and anatomic considerations. This entry zone is bordered caudally by the intramesencephalic path of the trochlear, laterally by the spinothalamic tract, and rostrally by the caudal margin of the brachium of the superior colliculus. METHODS: Four intrinsic midbrain lesions were operated upon via the safe entry zone using the infratentorial paramedian supracerebellar approach. All lesions involved the tegmentum and included an anaplastic astrocytoma, a metastatic brain tumor, a radiation necrosis, and a cavernous angioma. CMAP were bilaterally monitored from the inferior recti (for oculomotor function) and superior oblique (for trochlear nerve function) muscles. RESULTS: In three of four cases, CMAP related to the oculomotor nerve were obtained upon stimulation at the cavity wall after removal of the tumor. Stimulation at the surface of the quadrigeminal plate, however, did not cause any CMAP response. Using this monitoring as an indicator, the lesions were totally removed. CONCLUSIONS: In the surgery of tegmental lesions, CMAP monitoring from extraocular muscles is particularly helpful to prevent damage to crucial neural structures during removal of intrinsic lesions, but less so to select the site of the medullary incision. The approach via the lateral part of the colliculi is considered to be a safe route to approach the tegmental lesions.