Oculomotor nerve and muscle abnormalities in congenital fibrosis of the extraocular muscles

Congenital fibrosis of the extraocular muscles is an autosomal dominant congenital disorder characterized by bilateral ptosis, restrictive external ophthalmoplegia with the eyes partially or completely fixed in an infraducted (downward) and strabismic position, and markedly limited and aberrant residual eye movements. It has been generally thought that these clinical abnormalities result from myopathic fibrosis of the extraocular muscles. We describe the intracranial and orbital pathology of 1 and the muscle pathology of 2 other affected members of a family with chromosome 12-linked congenital fibrosis of the extraocular muscles. There is an absence of the superior division of the oculomotor nerve and its corresponding alpha motor neurons, and abnormalities of the levator palpebrae superioris and rectus superior (the muscles innervated by the superior division of the oculomotor nerve). In addition, increased numbers of internal nuclei and central mitochondrial clumping are found in other extraocular muscles, suggesting that the muscle pathology extends beyond the muscles innervated by the superior division of cranial nerve III. This report presents evidence that congenital fibrosis of the extraocular muscles results from an abnormality in the development of the extraocular muscle lower motor neuron system.     

动眼神经功能修复实验研究

目的研究成年SD大鼠动眼神经损伤后功能修复的机制。方法成年SD大鼠45只,随机分为4组:第一组:正常对照组(10只),动眼神经不损伤,其余35只大鼠均在海绵窦内切断右侧动眼神经主干,第二组为损伤对照组(5只)不予缝合,第三组和第四组立即用11-0无创缝线行端端对位缝合,定期观察动眼神经功能并进行神经组织学和解剖学研究。结果动眼神经包含粗细两种纤维,直径呈双峰分布。动眼神经核内运动神经元按功能不同集中分布(形成亚核)。动眼神经损伤后,核内的神经元数量减少(仅为损伤前的1/3)、亚核分布特征消失,再生轴突的数量明显增加,超过损伤前的水平,但以细纤维为主,双峰分布特征消失。瞳孔括约肌的功能恢复速度与最终的恢复水平明显优于眼外肌。结论动眼神经损伤后神经元的数量减少和非特异性增生及其再生轴突在效应器上的迷行分布影响了动眼神经的功能恢复。     

Oculomotor system of the weakly electric fish Gnathonemus petersii

The peripheral and central aspects of the extraocular system were studied in the weakly electric fish Gnathonemus petersii. All six extraocular muscles show a similar composition of large and small fibers grouped characteristically in the proximal and distal regions respectively. The exit of the three extraocular nerves from the brain is similar to that in other vertebrates. However, the intracephalic and intracranial course of the trochlear nerve is unusual, partly because of the extraordinary hypertrophy of the cerebellum. The three nerves course rostrally on the ventral brain surface; the trochlear nerve penetrates the orbital cavity separately from the two other nerves. The fiber-diameter spectrum of each extraocular nerve is bimodal; unmyelinated fibers were not observed in any of the nerves. The location of the extraocular motor nuclei was established by retrograde axonal transport of HRP or cobaltic-lysine complex. The oculomotor nucleus is situated ventral to the posterior pole of the magnocellular mesencephalic nucleus and the trochlear nucleus is found caudal and dorsal to this. The abducens nucleus is situated at the level of the octavolateral efferent nucleus and consists of a single group of cells on each side of the ventral tegmentum. The oculomotor nucleus of G. petersii shows a somatotopic organization. The superior rectus muscle receives a contralateral innervation whereas the inferior rectus and oblique muscles and the internal rectus muscles receive an ipsilateral innervation. The superior oblique muscle is innervated by contralateral trochlear motoneurons and the external rectus by ipsilateral abducens motoneurons. The majority of extraocular motoneurons have piriform perikarya and long beaded dendrites that extend laterally in the oculomotor and abducens nuclei and rostrally in the trochlear nucleus. The terminal dendritic portions of trochlear motoneurons widely overlap with oculomotor dendrites and perikarya. In all three nuclei the axon originates opposite to the main dendrite. Collaterals of the hairpin-bend abducens axons could be identified in a few cases. The oculomotor system of G. petersii appears basically similar to that of other teleosts; the differences observed concern mainly the structure of the abducens nucleus, the intracranial and intracephalic course of the trochlear nerve, and the relatively small number of axons in each nerve.     

SD大鼠动眼神经不同部位损伤后对靶器官特异性支配的实验研究

目的研究不同部位损伤对Sprague-Dawley（SD）大鼠动眼神经功能修复的影响及可能机制。方法实验Ⅰ组大鼠（n=24）经幕下、实验Ⅱ组（n=24）大鼠经眶上裂干预动眼神经，术后通过前庭眼反射评估眼外肌在垂直、水平方向的恢复程度。经右侧上直肌注射辣根过氧化酶（HRP），逆行追踪中脑动眼神经核团内神经元分布；48h后行动眼神经组织学、解剖学研究。结果实验Ⅰ组大鼠支配上直肌的神经纤维有45％～51％由对侧中脑运动神经元发出：实验Ⅱ组81％～87％由对侧中脑运动神经元发出，神经元在中脑的分布更接近正常大鼠。实验Ⅱ组大鼠眼外肌功能恢复程度明显优于实验Ⅰ组大鼠。结论动眼神经损伤部位距离眼外肌越近，最终的神经功能恢复水平越好，这可能与再生神经纤维通过损伤部位时的迷行程度相关。     

Fascicular arrangement within the oculomotor nerve MRI analysis of a midbrain infarct.

The fascicular arrangement of the oculomotor nerve within the midbrain is not adequately elucidated in humans. We treated a patient with a partial oculomotor palsy who had impaired adduction and supraduction on the left side, which were attributed to an ipsilateral lacunar infarct. CT and MRI revealed a discrete lesion in the centre of the midbrain tegmentum in the rostrocaudal plane. This case suggests that the oculomotor fibres for extraocular movement are located in the middle of the the midbrain, and supports the fascicular proximity of the superior and medial rectus muscles. The fascicular arrangement of the midbrain oculomotor nerve is speculated to be pupillary component, extraocular movement and eyelid elevation in that rostrocaudal order, based on the previous reports of neuro-ophthalmological impairment and MRI findings, which are analogous to the nuclear arrangement proposed by Warwick.     

Superior orbital fissure syndrome. Review of 130 cases.

Superior orbital fissure syndrome is a symptomatologic complex, consisting of retroorbital pain, paralysis of extraocular muscles, impairment of first trigeminal branches and frequent involvement of the optic nerve. From a review of 130 published cases including two personal observations, it appears that the clinical subdivisions and the several eponymic differentiations of this syndrome are unjustified on the basis of etiologic, therapeutic and prognostic elements. Only the presence--or absence--of optic signs may allow to hold the clinically useful distinction between the often 'benign' superior orbital fissure syndrome without optic nerve involvement, and the orbital apex syndrome where orbital exploration may be recommended. This review concludes that repeated neurosurgical and neuroradiologic investigations--with the exceptions of carotid angiography and orbital phlebography--can be avoided in such cases.     

Peripheral and central oculomotor organization in the goldfish, Carassius auratus

Peripheral and central oculomotor organization was studied in the goldfish. The sizes of the extraocular muscles were quantified by counting the fibers contained in a given muscle and by area measurements of the cross-sectional surfaces. All the muscles were of approximately similar size. Kinematics were determined by electrical stimulation of a given muscle. The macroscopic appearance and kinematics of the muscles had the characteristics of other lateral-eyed animals (e.g., rabbit). Locations of extraocular motor neurons were found by retrograde transport of horseradish peroxidase (HRP) following injections into individual extraocular muscles. The eye muscles were innervated by four ipsilateral (lateral rectus, medial rectus, inferior oblique, inferior rectus) and two contralateral (superior rectus, superior oblique) motor neuron pools. The oculomotor nucleus was found in the midbrain, at the level of the caudal zone of the inferior lobe of the hypothalamus. Inferior rectus motor neurons were located rostrally in the oculomotor nucleus, whereas medial rectus, superior rectus, and inferior oblique motor neurons were intermingled in its more caudal portions. All labelled cells were located dorsally and medially to the medial longitudinal fasciculus (MLF) in close proximity to either the floor of the ventricle or the midline region. Occasionally, motor neurons were interspersed within the fiber bundles of the MLF or the exiting fibers of the oculomotor nerve. The trochlear nucleus, containing superior oblique motor neurons, was found in the immediate lateral and caudal neighborhood of the oculomotor nucleus, where its rostral border overlapped with the caudal border of the latter. The abducens nucleus, containing lateral rectus motor neurons, was located in the posterior brainstem in the neighborhood of the vestibular nuclear complex. This nucleus was divided into a rostral and a caudal portion. The axons of ipsilaterally projecting motor neurons headed toward their respective nerve roots via the shortest possible route, as did the axons of superior rectus motor neurons, which crossed the midline without detour to enter the contralateral oculomotor nerve. In contrast, trochlear motor neuron axons arched around the dorsal aspect of the ventricle through the cerebellar commissure to reach the contralateral trochlear nerve. The morphology of individual motor neurons was visualized by intrasomatic injection of HRP. Cell somata had oblong shapes, and their large dendrites were oriented laterally and ventrally. The axons did not collateralize within the midbrain region or the oculomotor nerve as far as they could be traced.(ABSTRACT TRUNCATED AT 400 WORDS)     

Changes in the central representation of the extraocular muscles in the rat oculomotor nucleus after section and repair of the third cranial nerve

The anatomical location of motoneurons controlling the extraocular muscles within the oculomotor nucleus was investigated by injecting retrograde horseradish peroxidase (HRP) into individual eye muscles in control rats and in rats submitted to intracranial section and repair of the oculomotor nerve 6 months previously. Compared to the controls, the operated animals showed marked changes in the somatotopic organization of the oculomotor subnuclei. The possible nature of this re-arrangement is discussed.     

眶内电针治疗颅脑外伤后动眼神经麻痹的疗效及相关因素分析

目的 回顾眶内电针治疗颅脑外伤后动眼神经麻痹的病案,分析影响疗效的相关因素。方法 回顾性分析于我院接受眶内电针治疗的头外伤后动眼神经麻痹患者临床资料,使用多因素分析等方法对性别、年龄、颅脑损伤程度、动眼神经麻痹程度、眼运动神经麻痹评分、病程、治疗次数等可能影响疗效的因素进行分析。结果 90例患者中痊愈24例,显效及有效共46例,无效20例,总有效率77.8%。患者眼运动神经麻痹各项评分均明显减小,差异有统计学意义（P均<0.001）;其中眼睑运动和水平内收较下视运动、瞳孔散大及光反射改善明显。回归分析：GCS严重程度、病程为针灸有效的危险因素,（β=-3.835,P=0.016;β=-4.618,P=0.049）治疗次数为保护因素（β=0.406,P=0.006）;病程>90天的患者疗效差,针灸有效的可能性低,为≤ 90天的1/100（P<0.05）。结论 眶内电针可有效治疗头外伤后动眼神经麻痹,其中眼外肌较眼内肌恢复更好。其有效性受颅脑损伤程度,病程和治疗次数影响,GCS评分重,病程长、治疗次数少者针灸有效的可能性低。     

Hemorrhage in the oculomotor nerve as a complication of leukemia

Oculomotor paralysis of a patient with leukemia was revealed at autopsy to be caused by a hemorrhage in the oculomotor nerve. In a 63‐year‐old woman with pre‐B‐cell acute lymphatic leukemia, leukemic invasions occurred in her spinal cord and right oculomotor nerve during a hematological remission state. The oculomotor palsy was aggravated to complete paralysis during a leukemic relapse, which lasted until her death. An autopsy revealed a hemorrhage along with leukemic cells in the right oculomotor nerve at the segment in the upper orbital fissure. Although hemorrhagic oculomotor paralysis is a very rare complication, reports of its occurrence will likely increase with improved survival times of leukemia patients due to advances in chemotherapy.     

Third nerve palsies

The diagnosis and management of third nerve dysfunction vary according to the age of the patient, the characteristics of the third nerve palsy, and the presence of associated symptoms and signs. Third nerve palsies can result from lesions located anywhere from the oculomotor nucleus to the termination of the third nerve in the extraocular muscles within the orbit, and may be the herald manifestation of underlying neurological emergencies such as intracranial aneurysm, pituitary apoplexy, and giant cell arteritis. Recent advances in noninvasive neuroimaging facilitate early diagnosis, but the management of a patient presenting with isolated third nerve palsy remains a challenge.     

Reinnervation of the extraocular muscles in goldfish is nonselective

The selectivity of axonal regeneration to the extraocular muscles in teleosts has been reinvestigated by mapping, with retrogradely transported HRP, the motor pools of the muscles innervated by the oculomotor nerve. In normal goldfish, the motoneurons of the superior rectus, inferior rectus, and inferior oblique muscles formed discrete, nonoverlapping motor pools; the motor pool of the medial rectus muscle overlapped with those of the inferior oblique and inferior rectus muscles. In fish whose oculomotor nerve had regenerated (after intracranial transection), in contrast, many motoneurons in other, inappropriate motor pools reinnervated the superior rectus and inferior oblique muscles (the only muscles examined in lesioned animals). Furthermore, these inappropriate motoneurons continued to project to these muscles for at least 1 year. The oculomotor nerve and its molecular branches were examined by light and electron microscopy to determine the pathway by which axons regenerated to their muscles. Axons regenerated within the basal laminae of Schwann cells, which persisted in the distal nerve-stump after a lesion. After labeling the inferior oblique nerve with HRP in regenerated nerves, there were labeled axons in all of the muscular branches; this indicates that regenerating axons branched, which was confirmed by finding an increased number of myelinated axons in other, regenerated inferior oblique nerves. Thus, different branches of the same axons sometimes reinnervated different muscles. These results demonstrate that regenerating axons in the oculomotor nerve are misdirected to inappropriate muscles, and do not selectively reinnervate individual muscles, as had been previously suggested (Sperry and Arora, 1965).     

外伤性动眼神经麻痹的临床特点分析

目的总结轻型颅脑损伤所致动眼神经麻痹后的临床特点。方法通过眼外肌运动、眼睑活动、瞳孔大小分析20例轻型颅脑损伤患者动眼神经麻痹的严重程度及功能恢复,随访时间平均为14.2月(3个月~2年)。结果 15名男性患者和5名女性患者纳入此次研究。最常见的外伤原因是交通事故65.4%(13例);眼内肌麻痹是最常见的临床症状;上睑下垂、眼外肌麻痹和眼内肌麻痹的恢复率分别是95%(19例),83.3%(17例)和50%(10例)。结论眼球活动受限是影响轻型颅脑损伤动眼神经麻痹患者生活质量的一个主要因素;蝶骨骨折可能是一个潜在的机制参与了外伤性动眼神经麻痹的发生。     

The motor nuclei and sensory neurons of the IIIrd, IVth, and VIth cranial nerves in the monitor lizard, Varanus exanthematicus

The motor nuclei of the oculomotor, trochlear, and abducens nerves of the reptile Varanus exanthematicus and the neurons that subserve the sensory innervation of the extraocular muscles were identified and localized by retrograde and anterograde transport of horseradish peroxidase (HRP). The highly differentiated oculomotor nuclear complex, located dorsomedially in the tegmentum of the midbrain, consists of the accessory oculomotor nucleus and the dorsomedial, dorsolateral, intermediate, and ventral subnuclei. The accessory oculomotor nucleus projects ipsilaterally to the ciliary ganglion. The dorsomedial, dorsolateral, and intermediate subnuclei distribute their axons to the ipsilateral orbit, whereas the ventral subnucleus, which innervates the superior rectus muscle, has a bilateral, though predominantly contralateral projection. The trochlear nucleus, which rostrally overlaps the oculomotor nuclear complex, is for the greater part a comma-shaped cell group situated lateral, dorsal, and medial to the medial longitudinal fasciculus. Following HRP application to the trochlear nerve, almost all retrogradely labeled cells were found in the contralateral nucleus. The nuclear complex of the abducens nerve consists of the principal and accessory abducens nuclei, both of which project ipsilaterally. The principal abducens nucleus is located just beneath the fourth ventricle laterally adjacent to the medial longitudinal fasciculus and innervates the posterior rectus muscle. The accessory abducens nucleus has a ventrolateral position in the brainstem in close approximation to the ophthalmic fibers of the descending trigeminal tract. It innervates the retractor bulbi and bursalis muscles. The fibers arising in the accessory abducens muscles form a loop in or just beneath the principal abducens nucleus before they join the abducens nerve root. The afferent fibers conveying sensory information from the extraocular muscles course in the oculomotor nerve and have their perikarya in the ipsilateral trigeminal ganglion, almost exclusively in its ophthalmic portion.     

Painful ophthalmoplegia: the Tolosa-Hunt syndrome and orbital pseudotumor syndrome

We experienced 9 patients with "painful ophthalmoplegia", which included 7 cases of the Tolosa-Hunt syndrome (2 males and 5 females, with ages ranging from 36 to 65 years) and 2 cases of the orbital pseudotumor syndrome (2 females aged 42 and 68). The diagnosis of these syndromes was based upon Hunt's criteria and the presence of the intraorbital mass on the brain CT scan. Main manifestations of both syndromes were periorbital pain and ipsilateral oculomotor nerve palsies. Out of 9 cases, 1 patient with Tolosa-Hunt syndrome and 1 patient with the orbital pseudotumor syndrome had bilateral retro-orbital pain and ophthalmoplegia. Pain preceded the ophthalmoplegia except in one patient with Tolosa-Hunt syndrome. Total paralysis of the extraocular muscles supplied by the oculomotor nerve was noted in all the nine patients, and mydriasis was observed on the affected side in 4 of 7 patients with Tolosa-Hunt syndrome and 2 patients with the orbital pseudotumor syndrome. Neurological involvement was not only the oculomotor nerve but also the other cranial nerves; the optic nerve (in 4 cases with Tolosa-Hunt syndrome and 2 cases with the orbital pseudotumor syndrome), the abducens nerve (in 3 cases with Tolosa-Hunt syndrome and 1 case with the orbital pseudotumor syndrome), and the first division of the trigeminal nerve (in 2 cases with Tolosa-Hunt syndrome). Six patients with Tolosa-Hunt syndrome and 2 patients with the orbital pseudotumor syndrome had palpebral edema. Visual disturbance and palpebral edema were severer in the patients with the orbital pseudotumor syndrome. After corticosteroid hormone was administered, there was diminution of the pain within 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ischaemic oculomotor nerve palsy

Summary Of 61 patients with isolated third nerve palsy, 23 (38%) had the characteristic clinical features of an ischaemic oculomotor nerve palsy. The essential sign of this usually painful disorder of acute onset was a marked discrepancy between complete or severe paresis of the extraocular muscles innervated by the third nerve, and sparing of the pupillary sphincter. All patients had completely recovered within 3 months. Fourteen had a history or on follow-up had other cranial mononeuropathies. Except for two patients, all were above the age of 60 years. Of the 23 cases, 11 had diabetes mellitus and 8 an abnormal glucose tolerance test, while in 4 the latter was normal. Almost all had hypertension and were overweight, and half were smokers. In 18 patients, four or five vascular risk factors were present.     

Elasmobranch oculomotor organization: anatomical and theoretical aspects of the phylogenetic development of vestibulo-oculomotor connectivity

The oculomotor organization of two elasmobranch species, smooth dogfish (Mustelus canis) and little skate (Raja erinacea), was studied by investigating the extraocular muscle apparatus and the oculomotor motoneuron distribution. The macroscopic appearance of the eye muscles was similar to any lateral-eyed vertebrate species (e.g., goldfish, rabbit). The size of extraocular muscles was expressed by counting single muscle fibers and comparing cross-sectional areas of the extraocular muscles. There were significant differences in the number of fibers in the six extraocular muscles in dogfish, but not in skate. Fiber sizes varied considerably; thus, the number of fibers did not relate to cross-sectional areas. In the dogfish, no one pair of agonist-antagonist extraocular muscles was larger than the others, suggesting that there was no preference for eye movements in a particular plane of space. However, the lateral rectus was more than twice the size of most of the other muscles. In the skate, cross-sectional areas of the horizontal eye muscles were smaller than those of the vertical eye movers. This may indicate a reduced utilization of horizontal eye muscles, which may reflect the bottom-dwelling habitat and mode of locomotion of the skate. The distribution of the extraocular motoneurons was determined by injecting horseradish peroxidase (HRP) into single eye muscles. Medial rectus, superior rectus, and superior oblique motoneuron populations were located contralateral to their respective muscles. Lateral rectus, inferior rectus, and inferior oblique motoneurons were located ipsilateral to their muscles. This distribution is in contrast to almost all other vertebrates studied thus far, where medial rectus motoneurons are located ipsilateral to the muscle which they innervate. The oculomotor arrangement in elasmobranchs is likely to have consequences for the circuitry responsible for the production of conjugate compensatory eye movements in the horizontal plane. We hypothesize that, in contrast to other vertebrates, the basic elasmobranch vestibulo-ocular reflex pathway consists of three identically structured three-neuron-arcs connecting the three semicircular canals to their respective extraocular muscles. This innervation pattern may constitute a special feature of the elasmobranch brain or a phylogenetically older arrangement of eye movement pathways.     

Extra- and intracellular HRP analysis of the organization of extraocular motoneurons and internuclear neurons in the guinea pig and rabbit

The distribution of extraocular motoneurons and abducens and oculomotor internuclear neurons was determined in guinea pigs by injecting horseradish peroxidase (HRP) into individual extraocular muscles, the abducens nucleus, the oculomotor nucleus, and the cerebellum. Motoneurons in the oculomotor nucleus innervated the ipsilateral inferior rectus, inferior oblique, medial rectus, and the contralateral superior rectus and levator palpebrae muscles. Most motoneurons of the trochlear nucleus projected to the contralateral superior oblique muscle although a small number innervated the ipsilateral superior oblique. The abducens and accessory abducens nuclei innervated the ipsilateral rectus and retractor bulbi muscles, respectively. The somata of abducens internuclear neurons formed a cap around the lateral and ventral aspects of the abducens nucleus. The axons of these internuclear neurons terminated in the medial rectus subdivision of the contralateral oculomotor nucleus. At least two classes of guinea pig oculomotor internuclear interneurons exist. One group, located primarily ventral to the oculomotor nucleus, innervated the abducens nucleus and surrounding regions. The second group, lying mainly in the dorsal midline area of the oculomotor nucleus, projected to the cerebellum. Intracellular staining with HRP demonstrated similar soma-dendritic organization for oculomotor and trochlear motoneurons of both guinea pigs and rabbits. Dendrites of oculomotor motoneurons radiated symmetrically from the soma to cover approximately one-third of the entire nucleus, and each motoneuron sent at least one dendrite into the central gray overlying the oculomotor nucleus. In both species, a small percentage of oculomotor motoneurons possessed axon collaterals that terminated both within and outside of the nucleus. The dendrites of trochlear motoneurons extended into the medial longitudinal fasciculus and the reticular formation lateral to the nucleus. Our data on the topography of motoneurons and internuclear neurons in the guinea pig and soma-dendritic organization of motoneurons in the guinea pig and rabbit show that these species share common organizational and morphological features. In addition, comparison of these data with those from other mammals reveals that dendritic complexity (number of dendrites per motoneuron) of extraocular motoneurons exhibits a systematic increase with animal size.     

Brainstem terminations of extraocular muscle primary afferent neurons in the monkey

The central terminations of afferent nerve fibers from the extraocular muscles of the monkey were investigated by means of transganglionic transport of wheat germ agglutinin-conjugated horseradish peroxidase (WGA/HRP). Following injections of selected extraocular muscles with WGA/HRP, terminal labeling was apparent in the ipsilateral trigeminal sensory and cuneate nuclei. The density of trigeminal projections varied markedly from one rostrocaudal level to the next, being heaviest within the ventrolateral portion of pars interpolaris of the spinal trigeminal nucleus. A second extraocular muscle afferent representation was noted in ventrolateral portions of the cuneate nucleus. This projection was restricted to rostral portions of pars triangularis of the cuneate nucleus, partially overlapping the afferent termination from dorsal neck muscles. It is likely that some of the problems encountered in formulating conclusions regarding the functional role of extraocular muscle proprioception are due to a lack of detailed information of the central termination pattern of muscle afferents. Taken together, the present findings should provide a basis for further anatomical and physiological studies designed to elucidate the role played by extraocular muscle proprioceptors in vision and oculomotor control.