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Concept: Edinger-Westphal nucleus

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Aims : To derive a reliable estimate of the frequency of pupillary involvement and to study the patterns and course of anisocoria in conjunction with ophthalmoplegia in diabetes-associated oculomotor nerve palsy. Materials and Methods: In this prospective analytical study, standardized enrolment criteria were employed to identify 35 consecutive patients with diabetes-associated oculomotor nerve palsy who were subjected to a comprehensive ocular examination. Standardized methods were used to evaluate pupil size, shape, and reflexes. The degree of anisocoria, if present and the degree of ophthalmoplegia was recorded at each visit. Results: Pupillary involvement was found to be present in 25.7% of the total number of subjects with diabetic oculomotor nerve palsy. The measure of anisocoria was < 2 mm, and pupil was variably reactive at least to some extent in all cases with pupillary involvement. Majority of patients in both the pupil-involved and pupil-spared group showed a regressive pattern of ophthalmoplegia. Ophthalmoplegia reversed much earlier and more significantly when compared to anisocoria. Conclusions: Pupillary involvement in diabetes-associated oculomotor nerve palsy occurs in about 1/4 th of all cases. Certain characteristics of the pupil help us to differentiate an ischemic insult from an aneurysmal injury to the 3 rd nerve. Ophthalmoplegia resolves much earlier than anisocoria in diabetic oculomotor nerve palsies.

Concepts: Eye, Cranial nerves, Oculomotor nerve, Pupil, Oculomotor nerve palsy, Edinger-Westphal nucleus, Anisocoria, Mydriasis

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During wakefulness, pupil diameter can reflect changes in attention, vigilance, and cortical states. How pupil size relates to cortical activity during sleep, however, remains unknown. Pupillometry during natural sleep is inherently challenging since the eyelids are usually closed. Here, we present a novel head-fixed sleep paradigm in combination with infrared back-illumination pupillometry (iBip) allowing robust tracking of pupil diameter in sleeping mice. We found that pupil size can be used as a reliable indicator of sleep states and that cortical activity becomes tightly coupled to pupil size fluctuations during non-rapid eye movement (NREM) sleep. Pharmacological blocking experiments indicate that the observed pupil size changes during sleep are mediated via the parasympathetic system. We furthermore found that constrictions of the pupil during NREM episodes might play a protective role for stability of sleep depth. These findings reveal a fundamental relationship between cortical activity and pupil size, which has so far been hidden behind closed eyelids.

Concepts: Sleep, Eye, Protection, Parasympathetic nervous system, Non-rapid eye movement sleep, Pupil, Edinger-Westphal nucleus, Slow-wave sleep

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Acute oculomotor nerve palsy requires urgent exclusion of aneurysmal compression. We report a 62year old man with a transient right third nerve palsy with pupillary involvement, who was found to have neurovascular compression of the cisternal oculomotor nerve as it curved over a duplicated superior cerebellar artery on high resolution MR imaging. Direct vascular compression should be considered in patients with isolated cranial neuropathies in whom other pathologies have been excluded.

Concepts: Cerebellum, Cranial nerves, Oculomotor nerve, Trochlear nerve, Pupil, Oculomotor nerve palsy, Superior cerebellar artery, Edinger-Westphal nucleus

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Cyclic oculomotor nerve paresis is a rare and usually congenital disorder. It is characterized by unilateral third nerve paresis with periodic spasms causing eyelid elevation, miosis, and contraction of 1 or more of the extraocular muscles innervated by the third nerve. We report a 20-month-old girl who presented initially with a congenital partial right third nerve paresis without ptosis. She subsequently developed isolated cyclic spasms of the pupil followed several months later by permanent partial ptosis.

Concepts: Muscle, Eye, Cranial nerves, Oculomotor nerve, Pupil, Levator palpebrae superioris muscle, Edinger-Westphal nucleus, Anisocoria

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The oculomotor accessory nucleus, often referred to as the Edinger-Westphal nucleus [EW], was first identified in the 17th century. Although its most well known function is the control of pupil diameter, some controversy has arisen regarding the exact location of these preganglionic neurons. Currently, the EW is thought to consist of two different parts. The first part [termed the preganglionic EW - EWpg], which controls lens accommodation, choroidal blood flow and pupillary constriction, primarily consists of cholinergic cells that project to the ciliary ganglion. The second part [termed the centrally projecting EW - EWcp], which is involved in non-ocular functions such as feeding behavior, stress responses, addiction and pain, consists of peptidergic neurons that project to the brainstem, the spinal cord and prosencephalic regions. However, in the literature, we found few reports related to either ascending or descending projections from the EWcp that are compatible with its currently described functions. Therefore, the objective of the present study was to systematically investigate the ascending and descending projections of the EW in the rat brain. We injected the anterograde tracer biotinylated dextran amine into the EW or the retrograde tracer cholera toxin subunit B into multiple EW targets as controls. Additionally, we investigated the potential EW-mediated innervation of neuronal populations with known neurochemical signatures, such as melanin-concentrating hormone in the lateral hypothalamic area [LHA] and corticotropin-releasing factor in the central nucleus of the amygdala [CeM]. We observed anterogradely labeled fibers in the LHA, the reuniens thalamic nucleus, the oval part of the bed nucleus of the stria terminalis, the medial part of the central nucleus of the amygdala, and the zona incerta. We confirmed our EW-LHA and EW-CeM connections using retrograde tracers. We also observed moderate EW-mediated innervation of the paraventricular nucleus of the hypothalamus and the posterior hypothalamus. Our findings provide anatomical bases for previously unrecognized roles of the EW in the modulation of several physiologic systems.

Concepts: Nervous system, Neuron, Neuroanatomy, Hypothalamus, Brain, Parasympathetic nervous system, Pupil, Edinger-Westphal nucleus

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It was investigated whether alterations of the pupil’s light reflex might reflect Alzheimer’s disease (AD) pathology. Changes in the pupil’s system might be expected due to AD pathology present in the oculomotor system of the Edinger-Westphal nucleus, and a cholinergic deficit caused by degeneration of the nucleus basalis Meynert. A rather new method of repetitive light stimulation was applied assessing variations in pupil size, latency, and amplitude over time. We analyzed 44 healthy controls, 42 subjects with mild cognitive impairment (MCI), and 66 AD patients. AD and MCI showed a less pronounced pupil size decrease and amplitude increase over time than controls. A higher MMSE was associated with a higher increase of relative amplitude and greater decrease of latency in AD and MCI, and absolute amplitude increase in AD alone. Pupil size increase correlated with cerebrospinal fluid markers in AD. Summarized pupil light reflex is not stable under repetitive stimulation, but changes systematically and less pronounced in AD and MCI. Thus repetitive stimulation of the pupil’s response potentially indicates AD pathology.

Concepts: Alzheimer's disease, Time, Acetylcholine, Oculomotor nerve, Pupil, Mild cognitive impairment, Edinger-Westphal nucleus, Pupillary light reflex

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C boutons are large, cholinergic, synaptic terminals that arise from local interneurons and specifically contact spinal α-motoneurons (MNs). C boutons characteristically display a postsynaptic specialization consisting of an endoplasmic reticulum-related subsurface cistern (SSC) of unknown function. In the present work, by using confocal microscopy and ultrastructural immunolabeling, we demonstrate that neuregulin-1 (NRG1) accumulates in the SSC of mouse spinal MNs. We also show that the NRG1 receptors erbB2 and erbB4 are presynaptically localized within C boutons, suggesting that NRG1-based retrograde signaling may occur in this type of synapse. In most of the cranial nuclei, MNs display the same pattern of NRG1 distribution as that observed in spinal cord MNs. Conversely, MNs in oculomotor nuclei, which are spared in amyotrophic lateral sclerosis (ALS), lack both C boutons and SSC-associated NRG1. NRG1 in spinal MNs is developmentally regulated and depends on the maintenance of nerve-muscle interactions, as we show after nerve transection experiments. Changes in NRG1 in C boutons were also investigated in mouse models of MN diseases: i.e., spinal muscular atrophy (SMNΔ7) and ALS (SOD1(G93A)). In both models, a transient increase in NRG1 in C boutons occurs during disease progression. These data increase our understanding of the role of C boutons in MN physiology and pathology.-Gallart-Palau, X., Tarabal, O., Casanovas, A., Sábado, J., Correa, F. J., Hereu, M., Piedrafita, L., Calderó, J., Esquerda, J. E. Neuregulin-1 is concentrated in the postsynaptic subsurface cistern of C-bouton inputs to α-motoneurons and altered during motoneuron diseases.

Concepts: Nervous system, Neuron, Muscle, Amyotrophic lateral sclerosis, Cranial nerves, Chemical synapse, Atrophy, Edinger-Westphal nucleus

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Preganglionic motoneurons supplying the ciliary ganglion control lens accommodation and pupil diameter. In cats, these motoneurons make up the preganglionic Edinger-Westphal population, which lies rostral, dorsal and ventral to the oculomotor nucleus. A recent cat study suggested that caudal motoneurons control the lens and rostral motoneurons control the pupil. This led us to examine the morphology, ultrastructure and pretectal inputs of these populations. Preganglionic motoneurons retrogradely labeled by introducing tracer into the cat ciliary ganglion generally fell into two morphologic categories. Fusiform neurons were located rostrally, in the anteromedian nucleus and between the oculomotor nuclei. Multipolar neurons were found caudally, dorsal and ventral to the oculomotor nucleus. The dendrites of preganglionic motoneurons within the anteromedian nucleus crossed the midline, providing a possible basis for consensual responses. Ultrastructurally, several different classes of synaptic profiles contact preganglionic motoneurons, suggesting their activity may be modified by a variety of inputs. Furthermore, there were differences between the synaptic populations contacting the rostral and caudal populations, supporting the contention that these populations display functional differences. Anterogradely labeled pretectal terminals were observed in close association with labeled preganglionic motoneurons, particularly in the rostral population. Ultrastructural analysis revealed that these terminals, packed with clear, spherical vesicles, made asymmetric synaptic contacts onto motoneurons in the rostral population indicating these cells serve the pupillary light reflex. Thus, the preganglionic motoneurons found in the cat display morphologic, ultrastructural and connectional differences suggesting that this rostral preganglionic population is specialized for pupil control, while more caudal elements control the lens. J. Comp. Neurol., 2014. © 2014 Wiley Periodicals, Inc.

Concepts: Nervous system, Neuron, Eye, Oculomotor nerve, Pupil, Edinger-Westphal nucleus, Oculomotor nucleus, Pupillary light reflex

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There are two muscle fiber types in extraocular muscles: those receiving a single motor end plate, termed singly innervated fibers (SIFs), and those receiving multiple small terminals along their length, termed multiply innervated fibers (MIFs). In monkeys, these two fiber types receive input from different motoneuron pools: SIF motoneurons found within the extraocular motor nuclei, and MIF motoneurons found along their periphery. For the monkey medial rectus muscle, MIF motoneurons are found in the C-group, while SIF motoneurons lie in the A- and B-groups. We analyzed the somatodendritic morphology and ultrastructure of these three groups of macaque medial rectus motoneurons to better understand the structural determinants controlling the two muscle fiber types. The dendrites of A- and B-group motoneurons lay within the oculomotor nucleus, but those of the C-group motoneurons were located outside the nucleus, and extended into the preganglionic Edinger-Westphal nucleus. A- and B-group motoneurons were very similar ultrastructurally. In contrast, C-group motoneurons displayed significantly fewer synaptic contacts on their somata and proximal dendrites, and those contacts were smaller in size and lacked dense-cored vesicles. However, the synaptic structure of C-group distal dendrites was quite similar to that observed for A- and B-group motoneurons. Our anatomical findings suggest that C-group MIF motoneurons have different physiological properties than A- and B-group SIF motoneurons, paralleling their different muscle fiber targets. Moreover, primate C-group motoneurons have evolved a special relationship with the preganglionic Edinger-Westphal nucleus, suggesting these motoneurons play an important role in near triad convergence to support increased near work requirements. J. Comp. Neurol., 2013. © 2013 Wiley Periodicals, Inc.

Concepts: Muscle, Skeletal muscle, Primate, Neuromuscular junction, Motor neuron, Superior rectus muscle, Edinger-Westphal nucleus, Oculomotor nucleus

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Dissociated vertical divergence (DVD) is frequently associated with the infantile strabismus syndrome. There are different theories on the pathomechanism of this disorder, but none of them is generally accepted. Some authors believe that the slow upward movement of the covered eye is due to a different illumination of both retinae and consequently an unequal activity of the oculomotor nerve’s nuclei. In one hypothesis a predominance of crossing pupillary tract fibres from the pretectal area to motor and parasympathetic nuclei of the oculomotor nerve was supposed. The consequence of this abnormal pathway in the midbrain would be a pronounced contraction anisocoria in patients with DVD. In contraction anisocoria the directly illuminated pupil contracts more strongly than the contralateral pupil without any efferent defect. In a small study we compared direct and indirect pupillary light reflexes in 11 DVD patients and 10 normal subjects. We found no significant differences of contraction anisocoria between the two groups. The results do not support the hypothesis of a different pupillary tract pathway in the midbrain of patients with DVD.

Concepts: Eye, Theory, Mesencephalon, Oculomotor nerve, Pupil, Edinger-Westphal nucleus, Anisocoria, Ciliary ganglion