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.

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.

[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.

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.

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.

Transient trochlear nerve palsy following anterior temporal lobectomy for epilepsy.

Three of 22 patients (14%) who underwent anterior temporal lobectomy for treatment of medically intractable epilepsy at our institution from July 1987 through July 1993 experienced diplopia immediately after surgery. We found ipsilateral paresis of the superior oblique muscle in all three patients. Their ophthalmoplegia resolved completely within 14 weeks. We did not observe any new structural or ischemic changes on postoperative MRIs to account for their deficits. Trochlear nerve palsy--not oculomotor nerve palsy, as is reported in most reference texts--is a relatively common cause of transient diplopia following temporal lobectomy. Indirect (ie, traction) injury of the trochlear nerve is a plausible mechanism that would explain this complication.

Brown's syndrome.

Brown's syndrome is a well-recognized clinical disorder of ocular motility manifesting most notably a restriction of active and passive elevation in adduction. The original name, "superior oblique tendon sheath syndrome," is no longer appropriate, since it has been shown that the tissue surrounding the anterior superior oblique tendon is blameless as a restrictive force. "True" and "simulated" as descriptive modifiers should also be discarded, as they relate to the disproven sheath concept. Brown's syndrome occurs as a congenital or acquired, constant or intermittent condition; the common link is restriction of free movement through the trochlea pulley mechanism. The various etiologic theories are reviewed and the spectrum of medical and surgical treatments are described and evaluated. Evidence suggests that subtypes of Brown's syndrome lie on a single continuum and that spontaneous resolution occurs in each group, probably more often than previously recognized. A simplified classification scheme is encouraged and possible future directions in Brown's syndrome research are introduced.

The injury response of nerve fibres in the anterior medullary velum of the adult rat.

The injury response of myelinated central nervous system (CNS) axons was documented in the anterior medullary velum (AMV) of the adult rat. Study of silver-stained AMV whole-mounts revealed sprouting of injured axons as early as 14 h post-lesion (hpl), with a complex network of fibres formed by 48 hpl. Signs of fibre degeneration were also apparent from 48 hpl, increasing in extent until 15 days post-lesion (dpl). Fragmentation was largely confined to specific fibre bundles, constituted by the distal portions of severed axons. Although some degeneration of regenerated axons was evident from 15-20 dpl, many remained intact beyond this time, particularly in the area adjacent to the exit of the trochlear nerve, where most regenerated fibres penetrated the ipsilateral trochlear nerve. Counts of HRP filled neurons in the trochlear nucleus after injection of the superior oblique muscle showed that axons entering the IVth nerve rootlet were exclusively ipsilateral trochlear fibres. Less than 50% regenerated; most other severed axons degenerated. The few axons remaining in the AMV may have been fibres, undamaged by the original lesion, which normally course longitudinally through the ipsilateral AMV. These results show that IVth nerve fibres preferentially enter IVth nerve rootlets and, in so doing, survive the effects of injury. Most other CNS axons in the AMV which do not enter the trochlear root probably degenerate.

Intraoperative recordings of evoked extraocular muscle activities to monitor ocular motor nerve function.

During 22 operations in 18 patients, we stimulated the ocular motor nerves electrically, intracranially, and recorded compound muscle action potentials (CMAP) directly from the extraocular muscles with a ring electrode that we developed. Recording electrodes were applied in 52 instances to the superior rectus, medial rectus, superior oblique, or lateral rectus muscle and to the levator palpebrae superioris in 2 instances; CMAP were recorded successfully from 22 muscles. Evoked CMAP were not recorded in 2 instances because of problems with recording equipment; in the remaining 30 instances, no evoked CMAP were recorded because 1) the oculomotor or abducens nerve was not exposed during the operation; or 2) the recording electrode on the superior oblique muscle had not been properly placed to record trochlear nerve CMAP. Placement of this electrode is difficult. Ocular motor nerve function was analyzed preoperatively and postoperatively to evaluate the usefulness of this intraoperative electrophysiological monitoring method in preventing damage to ocular motor nerves. The results of this study showed that monitoring enables surgeons to locate precisely ocular motor nerves that would otherwise have been overlooked and thus possibly injured during surgery. Monitoring results also confirmed the surgeons' visual findings, thus helping the surgeons operate with greater confidence. Further, intraoperative monitoring provided us with some insights into the pathophysiology of ocular motor nerve dysfunction caused by skull base lesions; we documented electrophysiologically the occurrence of the slowing of conduction in the ocular motor nerves. We conclude that monitoring ocular motor nerve CMAP can reduce the incidence of surgical complications such as functional blindness due to inadvertent sectioning of one of these nerves and that it would be worthwhile to conduct studies of this technique in many more cases to validate our findings.

Surgically created fourth-third cranial nerve communication: temporary success in a child with bilateral third nerve hamartomas. Case report.

Shortly after birth, an otherwise healthy infant developed eye deviation and ptosis due to a hamartomatous lesion of the interpeduncular segment of the right oculomotor nerve. The left nerve became similarly involved when the child was 1.5 years of age. Direct nerve repair was not possible. Instead, the trochlear nerve was divided and its proximal end was attached to the distal end of the third nerve. Elevation of the upper eyelid and partial adduction of the eye developed gradually over the ensuing 3 to 5 months. Both functions were lost after an additional 2 months, presumably as a result of tumor recurrence or neuroma formation. This case report shows that surgically created fourth-third cranial nerve communication is feasible and may merit consideration under similar circumstances.

[Fisher's one-and-one half syndrome. Involvement of the 6th cranial nerve nucleus and association with paralytic pontine exotropia]. / Syndrome un et demi de Fisher. Atteinte du noyau du VI associée à une exotropie pontine paralytique.

Total lateral paralysis in a case of "One and half" Fisher's syndrome accompanied by paralytic pontine exotropia is described. Oculographic investigation indicates involvement of the nucleus of the VIth cranial nerve. Paralytic pontine exotropia, may therefore be encountered where the VIth nucleus is involved.

The evaluation and treatment of extraocular motility deficits.

Binocular diplopia, monocular diplopia and oscillopsia may be manifestations of skull base lesions or may result from skull base surgery. An ophthalmologic perspective on the diagnosis and treatment of these extraocular motility deficits is reviewed.

Measurement of vertical deviations in different gaze positions in patients with a superior oblique palsy.

Objective measurements in eight consecutive patients with an isolated congenital superior oblique palsy using a head tilt technique, with gaze directed toward a fixed distance target, and a second technique with gaze directed at a movable near object in different fields of gaze each identified the same oblique position of maximal vertical deviation. We call the latter technique "field-directed." In distinction to the controversy that exists as to which method correctly diagnoses an isolated superior oblique palsy, either technique can be used to direct the surgical correction of this palsy. Superimposing a head tilt on the field-directed technique affected measurements in 16 of the 20 instances where tested. Despite the necessity of avoiding an inadvertent head tilt the field-directed technique is considerably easier to perform and more comfortable for the patient to endure in determining the position of maximal vertical deviation.

Idiopathic superior oblique palsies in children.

The records of 110 patients with superior oblique palsy seen at the Boston Children's Hospital between 1966 and 1988 were reviewed. Patients with identifiable orbital or neurological disorders affecting the fourth cranial nerve or with a history of head trauma preceding their superior oblique palsy were excluded from analysis. Patients were also excluded because of prior surgery elsewhere or insufficient diagnostic information. The remaining 63 patients were considered to have idiopathic superior oblique palsies. All 63 patients presented with unilateral palsies. All had incomitant hypertropia of the affected eye, greater on gaze to the contralateral side and increased by ipsilateral head tilt. Left eyes were affected in 41 patients. The age at first ophthalmological examination was spread over the first 20 years, with heavier representation in the first 5 years and decreasing numbers in each succeeding 5-year interval. Only one patient was found to have a masked bilateral superior oblique palsy following surgery for an apparent unilateral palsy. A distinction is made between unmasking a bilateral superior oblique palsy and surgical overcorrection of a unilateral palsy. The predominant unilaterality of idiopathic superior oblique palsies is in contrast to the reported frequency of bilaterality in traumatic cases.