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PubMed1997

Multiple sclerosis, the great masquerader: an atypical ocular presentation.

BACKGROUND: Multiple sclerosis (MS) is the most common chronic disease of the central nervous system and is pleomorphic in it presentations. The optic pathways are frequently involved, and the classic ocular abnormality is optic neuritis. METHODS: A case is presented of a 23-year-old woman in whom optic neuropathy developed and multiple sclerosis was diagnosed by neuroradioimaging, in spite of her lack of awareness of vision loss. RESULTS: The demyelinating lesions in MS may develop anywhere in the visual system and produce a variety of visual defects. Magnetic resonance imaging (MRI) is the most sensitive method for demonstrating these lesions. CONCLUSION: The cause of MS is unknown, but current opinion holds that autoimmunity--perhaps induced by viral infection--is likely to be implicated in its etiopathogenesis. Currently, no method for prevention of MS is known.

Administration, Oral↗

PubMed1996

Pediatric orbital and visual pathway lesions.

This article presents the clinical and imaging aspects of some common and important orbital and optic pathway lesions occurring in childhood. Lesions that arise outside of and encroach on the orbit and visual pathways are included. Abnormalities intrinsic to the globe are covered elsewhere in this issue.

Adolescent↗

PubMed1981

Retinal recipient nuclei in the painted turtle, Chrysemys picta: an autoradiographic and HRP study.

Retinofugal pathways in the painted turtle were examined with autoradiographic and HRP methods. The majority of the retinal fibers decussate at the optic chiasm and course caudally to terminate in 12 regions of the diencephalon and mesencephalon. The pars dorsalis of the lateral geniculate nucleus is the densest target in the thalamus. Two nuclei dorsal to pars dorsalis--the dorsal optic and dorsal central nuclei--receive optic input. Three nuclei ventral to pars dorsalis and retinal targets--the ventral geniculate nucleus, nucleus ventrolateralis pars dorsalis, and nucleus ventrolateralis pars ventralis. Contralateral fibers course through the pretectum where they terminate in nucleus geniculatis pretectalis, nucleus lentiformis mesencephali, nucleus posterodorsalis, and the external pretectal nucleus. Retinal fibers also terminate within the superficial zone of the optic tectum. HRP material demonstrates three optic fiber layers--laminae 9, 12, and 14. Optic fibers leave the main optic tract as a distinct accessory tegmental optic pathway and terminate in the basal optic nucleus. Ipsilateral retinal terminals occur in a pars dorsalis and a pars ventralis of the lateral geniculate nucleus, the dorsal optic nucleus, nucleus posterodorsalis, the basal optic nucleus, and in laminae 9 and 12 of the optic tectum. Rostrally, the ipsilateral tectal fibers occupy two zones along the medial and lateral tectal roof; these zones converge caudally and are continuous along the caudal wall of the tectum.

Animals↗

PubMed1978

Optic nerve gliomas. I. Clinical diagnosis and pathology.

At the National Institute of Neurosurgery a team of ophthalmologists and neurosurgeons has for 20 years been collaborating in the research and treatment of optic nerve gliomas. Among 34 patients, 30 were under the age of 20 years, and 20 under the age of 10 years. Of the 20 patients younger than 10 years, 16 were girls. The clinical symptoms were classified into three groups: I. Unilateral visual impairment with unilateral axial proptosis (16 patients), strabismus (6 cases), and typical X-ray findings of the skull. II. Uni- or bilateral visual impairment without proptosis (12 patients), depressed vision in the homolateral eye (9 patients), hemianopia (2 out of 4 examined patients) and hemiparesis (6 cases). III. Uni- or bilateral visual impairment without proptosis but with hormonal or metabolic disturbances (6 patients). Carotid angiography and PEG were performed in groups II and III and revealed a picture that is characteristic of suprasellar tumours. 99mTc pertechnetate scanning was done in six cases and showed isotope accumulation in the tumour in five. Pathologically, considering also the clinical aspects, two types of localization merit consideration: 1. The relationship between the tumour and the optic nerve (tumours growing within and extending beyond the optic pathways, respectively) and 2. The site of the tumour within the optic nerve (intraorbital, intraorbital and intracranial, intracranial only, chiasmal, and diffuse). Our data of histology and tissue culture prove the benign nature of the tumour even in the recurrences.

Adolescent↗

PubMed1994

Glial domains and axonal reordering in the chiasmatic region of the developing ferret.

This study has examined the developing glial architecture of the optic pathway and has related this to the changing organization of the constituent axons. Immunocytochemistry was used to reveal the distribution of glial profiles, and DiI was used to label either radial glial profiles or optic axons. Electron microscopy was used to determine the distribution of glial profiles, axons, growth cones, and wrists at different locations along the pathway. Three different glial boundaries were defined: Two of these are revealed as changes in the distribution of vimentin-immunoreactive profiles occurring in the prechiasmatic optic nerve and at the threshold of the optic tract, respectively, and one by the presence of glial fibrillary acidic protein (GFAP)-immunoreactive profiles at the chiasmatic midline. The latter, midline boundary may be related to the segregation of nasal from temporal optic axons. The boundary at the threshold of the optic tract coincides with the segregation of dorsal from ventral optic axons that emerges at this location in the pathway. The segregation of old from young optic axons is shown to occur only gradually along the pathway. Glial profiles are most frequent in the deeper parts of the tract, coursing parallel to the optic axons and orthogonal to their usual radial axis. These are suggested to arise from later-growing radial glial fibers that are diverted to grow amongst the older optic axons. Those glial profiles may subsequently impede axonal invasion, thus creating the chronotopic reordering by forcing the later-arriving axons to accumulate superficially.

Animals↗

PubMed1985

Vision and the skin camouflage reactions of Ambystoma larvae: the effects of eye transplants and brain lesions.

Salamander larvae typically adapt their dermal melanophores to achieve camouflage, and it has been known for some time that removal of the eyes abolishes the response. Here we survey the contribution of the optic system to the bright and dark camouflage reactions and report that: the stimulus depends on an interaction between the direct and reflected light; an eye mounted atop the head and oriented vertically tended not to support camouflage, even though the animal responded to visual cues and learned a vision-dependent task; deviating the transplanted eye off the vertical axis enhanced the recovery of camouflage reactions; amputating or reorienting the telencephalon, epithalamus, pretectum or tectum did not abolish either camouflage reaction whereas lesions of the ventral optic pathway blocked brightening; transection near the midbrain-hindbrain junction--well posterior to known optic terminals--retarded the dark reaction; when the latter lesion was combined with disconnection of the telencephalon and epithalamus, contrary to predictions from the lesions executed separately, the animals lost the bright reaction; the hypophysis is necessary for darkening, but the organ supported this reaction even though detached, displaced or reoriented; and the pineal body was not essential for the grosser aspects of camouflage in Ambystoma larvae but may play an adjunctive role in fine tuning.

Ambystoma↗

PubMed2004

Dynamic expression patterns of Robo (Robo1 and Robo2) in the developing murine central nervous system.

The Robo family of molecules is important for axon guidance across the midline during central nervous system (CNS) development in invertebrates and vertebrates. Here we describe the patterns of Robo protein expression in the developing mouse CNS from embryonic day (E) 9.5 to postnatal day (P) 4, as determined by immunohistochemical labeling with an antibody (S3) raised against a common epitope present in the Robo ectodomain of Robos 1 and 2. In the spinal cord, midline-crossing axons are initially (at E11) S3-positive. At later times, midline Robo expression disappears, but is strongly upregulated in longitudinally running postcrossing axons. It is also strongly expressed in noncrossing longitudinal axons. Differential expression of Robo along axons was also found in axons cultured from E14 spinal cord. These findings resemble those from the Drosophila ventral nerve cord and indicate that in vertebrates a low level of Robo expression occurs in the initial crossing of the midline, while a high level of expression in the postcrossing fibers prevents recrossing. Likewise, Robo-positive ipsilateral axons are prevented from crossing at all. However, in the brain different rules appear to apply. Most commissural axons including those of the corpus callosum are strongly S3-positive along their whole length from their time of formation to postnatal life, but some have more complex age-dependent expression patterns. S3 labeling of the optic pathway is also complex, being initially strong in the retinal ganglion cells, optic tract, and chiasma but thereafter being lost except in a proportion of postchiasmal axons. The corticospinal tract is strongly positive throughout its course at all stages examined, including its decussation, formed at about P2 in the central part of the medulla oblongata.

Aging↗

PubMed1983

Efferent projections of the visual Wulst upon the nucleus of the basal optic root in the pigeon.

Efferent projections of the visual Wulst upon the nucleus of the basal optic root (nBOR) were investigated using various neuroanatomical approaches: optical and EM orthograde degeneration methods (following visual Wulst ablation), radioautographic and HRP techniques (following injection of various tracers within the visual Wulst). The radioautographic and electron microscope degeneration experiments clearly demonstrated a visual Wulst projection upon the ipsilateral nBORl and the lateral portions of nBORd and nBORp. The pigeon's hyperstriato-nBOR projection is compared to a similar descending visual cortico-accessory optic pathway in mammals and its possible role in the control of oculomotor function is discussed.

Animals↗

PubMed2002

[A case of traumatic chiasmal syndrome presenting with bitemporal upper quadrantanopsia].

A 22-year-old woman was involved in a motor vehicle accident and suffered a craniofacial injury. The patient was treated conservatively with a diagnosis of cerebral contusion in the frontal base confirmed with MR images. When the patient regained consciousness one week after the accident, she had a complete form of bitemporal upper quadrantanopia. A bone window level CT scan showed a linear fracture in the middle of the frontal base running longitudinally and extending posteriorly down to the sella turcica and clivus. Axial MR images parallel to the optic pathway revealed a T2 bright lesion in the anterior half of the optic chiasm. The patient recovered gradually and returned to her previous life-style six months later without complaining of diplopia, but her visual field defect was left unchanged. Traumatic chiasmal syndrome is rare and usually presents bitemporal hemianopsia. Very rarely, bitemporal quadrantanopsia has been reported. Given the anatomical structure that the neural fibers from the lower nasal part of the retina run posteriorly in the optic nerve and cross the anterior half of the optic chiasm to enter the contralateral optic tract, the lesion in the optic chiasm seen in the MR images seemed to be the causative lesion of bitemporal upper quadrantanopsia in our patient. The optic chiasm appeared to be injured by a laterally stretching force exerted in an antero-posterior direction when the medial basal fracture occurred.

Accidents, Traffic↗

PubMed1988

Visual system of the channel catfish (Ictalurus punctatus): III. Fiber order in the optic nerve and optic tract.

In channel catfish the ganglion cell axons leave the retina via a ring of approximately 13 separate optic papillae. Each papilla serves an area of retina extending from the central zone of the retina to the periphery. Papillae located at a dorsal position in the ring serve exclusively dorsal retina. Ventrally located papillae, however, have an exaggerated peripheral retinal representation, so that they serve mostly ventral retina but also some areas of peripheral retina dorsal to the nasal and temporal poles. The ganglion cell axon bundles departing from the retina via individual papillae were labelled with horseradish peroxidase, and sections of the optic pathway were examined to reveal the topographic organization of the fibers. The topographic order of the optic nerve was dissimilar to that of cichlids and goldfish. Fibers from individual papillae remained together throughout the optic nerve. Close to the optic nerve head, the papillae were arranged as a continuum around the U-shaped optic nerve, without the discontinuity in the representation of the ventral retina seen in other fish. Fibers associated with the dorsal papillae were located at the tip of the caudolateral arm of the U, and fibers from ventral papillae were on the rostromedial arm. Fibers from nasally and temporally located papillae were found on the base of the U. By the level of the optic chiasm the U shape had flattened out but retained the relative ordering of the papillae. Rotation of the nerve as it became the optic tract brought the representation of the ventral papillae to the dorsal pole of the tract, and the dorsal papillae to the ventral tract. It was only in the optic tract that rearrangement of fibers became apparent. As described above, the axons of some ganglion cells in dorsal, peripheral retina left the retina and travelled through the optic nerve with axons from extreme ventral retina. In the optic tract, these dorsal fibers joined the main body of fibers from the dorsal retina. The significance of these observations for theories of fiber rearrangement is discussed.

Animals↗

PubMed1997

Essential role of heparan sulfates in axon navigation and targeting in the developing visual system.

Heparan sulfate (HS) is abundant in the developing brain and is a required co-factor for many types of fibroblast growth factor (FGF) signaling in vitro. We report that some HSs, when added exogenously to the developing Xenopus optic pathway, severely disrupt target recognition causing axons from the retina to bypass their primary target, the optic tectum. Significantly, HS sidechains from a neuroepithelial perlecan variant that preferentially bind FGF-2, HS(FGF-2), cause aberrant targeting, whereas those that preferentially bind FGF-1 do not. Charge-matched fragments of HS(FGF-2) show that the mistargeting activity associates with the FGF-binding fragments. Heparitinase removal of native HSs at the beginning of optic tract formation retards retinal axon elongation; addition of FGF-2 restores axon extension but axons lose directionality. Late HS removal, after axons have extended through the tract, elicits a tectal bypass phenotype indicating a growth promoting and guidance function for native HSs. Our results demonstrate that different HS sidechains from the same core protein differentially affect axon growth in vivo, possibly due to their distinct FGF-binding preferences, and suggest that growth factors and HSs are important partners in regulating axon growth and guidance in the developing visual system.

Animals↗

PubMed2000

[Exploration of retro-chiasmatic visual pathways in human albinism].

PURPOSE: Several research studies have explored the abnormal crossing of the retinogeniculate and geniculocortical optic pathways in human albinos. This prospective study has dealt with visual evoked potentials (VEPs) of human subjects to identify the percentage of albinos with asymmetric VEPs. PATIENTS AND METHODS: A series of 16 albino patients ranging in age from 6 to 37 years were examined. They had measurable visual acuity, with or without nystagmus. Diffusion of flash stimuli not allowing selective study of the two visual pathways (direct and crossed), two stimulation patterns were used for VEP recordings: monocular full open field then hemi-field stimulation to isolate the activity of each visual pathway. ANALYSIS: In the normally pigmented subject, fibers derived from the nasal half of the retina of each eye decussate at the chiasma, while temporal retinal fibers are uncrossed and project to the ipsilateral hemisphere. In albinos, the majority of temporal retinal fibers subserving the nasal field (from fixation to an eccentricity of about 20 degrees ) anomalously cross with the nasal retinal fibers. Therefore with monocular stimulation, the evoked visual response should be obtained only in the contralateral hemisphere. The asymmetry, morphology and latency for the first major positive peak and the amplitude of the VEP were examined and compared with the normal population. CONCLUSION: We managed to demonstrate the characteristic VEP asymmetry only in 3 out of the 16 patients. The results presented herein lead to question the absolute validity of VEP abnormality in diagnosis of albinism for clinical purposes.

Adolescent↗

PubMed1998

Protection of visual pathway in gamma knife radiosurgery for craniopharyngiomas.

Craniopharyngiomas present a major challenge to Gamma Knife radiosurgery (GKRS) due to their proximity to the optic apparatus. Based on observations of the evolving tumoral change on MRI and clinical results, an optimization of the treatment strategy and dose selection is possible. From March 1993 to September 1996, 21 patients with craniopharyngiomas were treated by GKRS. Every patient received stereotactic MRI exclusively for targeting and dose planning. The tumor and adjacent structures, including optic nerves, chiasm, and tracts were carefully identified and delineated on sagittal, coronal and axial films. The tumor volume ranged from 0.3 to 28 ml (average 9 ml). We purposefully apply multiple isocenters (average 9.1 shots) to create an isodose curve that covered the tumor optimally while sparing the optic pathway. The marginal dose prescribed was 9.5 to 16 Gy (50%). The maximal dose was 19 to 32 Gy. The maximal dose to the optic apparatus was 3.2 to 12.5 Gy. After GKRS, all patients were followed up clinically every month. MR studies were conducted every six months with the same techniques on the same scanner to investigate evolution of tumor volume and any adverse radiation effect. The follow-up period ranged from 6 to 40 months (mean: 18.4, median: 19). All patients were followed more than 6 months. Nineteen out of 21 cases (90.5%) achieved tumor control; that is, 18 tumor shrinkage (volume reduction: 15-95%) and 1 stabilized tumor growth. Among these 21 patients, 7 had improved visual acuity or visual field after GKRS, and the rest remained stable. Two patients developed mild T2 change on MRI without any endocrinological disturbance or visual impairment. Protection of the visual pathway can be secured by a sophisticated delineation on 3-dimensional stereotactic images with multiple-shot dose planning. Craniopharyngiomas with tumor volume up to 25 ml were treated safely and effectively, because the dose to the optic apparatus was kept as low as possiby this strategy. Further follow-up is needed to determine the highest tolerable dose to surrounding critical structures and the long-term outcome of tumor control.

Adolescent↗

PubMed2006

Slit proteins regulate distinct aspects of retinal ganglion cell axon guidance within dorsal and ventral retina.

An early step in the formation of the optic pathway is the directed extension of retinal ganglion cell (RGC) axons into the optic fiber layer (OFL) of the retina in which they project toward the optic disc. Using analysis of knock-out mice and in vitro assays, we found that, in the mammalian retina, Slit1 and Slit2, known chemorepellents for RGC axons, regulate distinct aspects of intraretinal pathfinding in different regions of the retina. In ventral and, to a much lesser extent, dorsal retina, Slits help restrict RGC axons to the OFL. Additionally, within dorsal retina exclusively, Slit2 also regulates the initial polarity of outgrowth from recently differentiated RGCs located in the retinal periphery. This regional specificity occurs despite the fact that Slits are expressed throughout the retina, and both dorsal and ventral RGCs are responsive to Slits. The gross morphology and layering of the retina of the slit-deficient retinas is normal, demonstrating that these distinct guidance defects are not the result of changes in the organization of the tissue. Although displaced or disorganized, the aberrant axons within both dorsal and ventral retina exit the eye. We also have found that the lens, which because of its peripheral location within the developing eye is ideally located to influence the initial direction of RGC axon outgrowth, secretes Slit2, suggesting this is the source of Slit regulating OFL development. These data demonstrate clearly that multiple mechanisms exist in the retina for axon guidance of which Slits are an important component.

Adaptation, Physiological↗

PubMed1989

Developmental changes in phosphorylation state of neurofilament proteins in the chick embryonic optic nerve.

Developmental changes in the phosphorylation state of neurofilament proteins (NFPs) in the chick embryonic optic nerve were histochemically and biochemically studied using monoclonal antibody (MAb) 82E10 specific to the highly phosphorylated components of high (180K)- and middle (160K)-molecular-weight subunits of neurofilament (NF) in the chicken. Cross sections of developing embryonic optic nerve were studied by enzyme immunohistochemistry using this MAb. The staining pattern showed marked changes with the developmental stage. In 6-day embryos (E6) the entire cross section was stained, whereas in E10 only about a ventroposterior half of the cross section was stained. In E14 nearly the entire area of the cross section became unstained. Thereafter, the immunoreactivity reappeared and gradually increased, such that in E20 the entire cross section became immunopositive again. Electrophoretic and immunoblot analyses were made on optic nerves dissected out of embryos of various stages. The 82E10 immunoreactivity at the position of NF-M underwent a transient loss in E14 in parallel with the time course of histochemical change. Two-dimensional gels stained for protein further showed that the highly phosphorylated form of NF-M is transiently lost from embryonic optic nerve in E14, while the less phosphorylated form persists throughout the embryonic developmental stages. In order to understand the orderly loss of the 82E10 immunoreactivity in relation to retinotopic and chronotopic organizations of the fibers in the embryonic optic nerve, retinal injection of a fluorescent dye DiI as an anterograde tracing marker for selected fibers was utilized. An ordered arrangement of the fibers was present within the embryonic optic pathway, suggesting that the orderly loss of the 82E10 immunoreactivity in the embryonic optic nerve reflects the chronological order of the optic axons. These changes in the phosphorylation state of NFPs in the embryonic optic nerve presumably reflect dynamic changes of the neuronal cytoskeleton at certain stages during development.

Alkaline Phosphatase↗

PubMed2003

Growth and pubertal disorders in neurofibromatosis type 1.

The first textbook of Pediatric Endocrinology in the early 1950s reported an association of neurofibromatosis type 1 (NF1) and precocious puberty (PP) and/or short stature. Recent studies have indicated that children with NF1 grow normally until puberty; thereafter height velocity and relative height (SDS or percentiles) decreases with respect to healthy peers, reaching a mean adult height close to the 25th percentile for the general population. Moreover, the percentage of patients with true short stature (<3rd percentile) increases from childhood (5%) to late puberty (20-30% in literature, 18% in our study), and final height is significantly below the genetic target and predicted adult height calculated just before or at the beginning of puberty. Finally, among the shortest patients (<10th percentile) there is a high incidence of severe complications, such as CNS tumors, huge plexiform neurofibromas and severe scoliosis. Precocious puberty is a frequent complication of NF1, and occurs mainly in association with optic pathway tumors (OPT); however, occasionally it has been reported in the absence of optic gliomas, probably with a similar incidence as in the general population. GnRH agonist therapy must be decided individually as in some patients further growth could be normal and/or treatment would not improve final height. In the presence of early pubertal signs, an OPT must be ruled out. In addition to PP, delayed puberty has been frequently reported in NF1. In a study of 123 girls with NF1, we found that the mean age at menarche (13.0 +/- 1.9 yr) was later than in their mothers (12.7 +/- 1.4 yr) and in the general population (12.4 +/- 1.2 yr; p <0.05), with a very high incidence of delayed menarche (>2 SD): 16% vs 6.8% (mothers) vs 3.4% (controls) (p <0.01). In conclusion, growth and puberty present unusual patterns in NF1, often with true pathological findings increasing medical and psychological problems.

Body Height↗

PubMed1994

Changes in fiber order in the optic nerve and tract of rat embryos.

In order to define the extent to which retinotopic order in the optic pathways may contribute to fiber segregation at the chiasm or to the formation of central maps, the arrangement of fibers in the optic nerve and tract of rat embryos, on embryonic days 16.5 and 18.5, has been studied by placing a small granule of DiI in one of the four quadrants of the retina and tracing the filled fibers through transverse sections of the retinofugal pathway with confocal microscopy. There is a distinct quadrant-specific order in the optic stalk immediately behind the eye, with fibers from the ventral nasal, dorsal nasal, dorsal temporal, and ventral temporal retina arranged sequentially across the rostrocaudal axis of the cross section of the stalk. However, this distinct order is not maintained very far. There is a gradual increase in the degree of overlap between fibers from the different quadrants as the fibers pass towards the chiasm. The dorsal groups of fibers intermingle extensively along almost the entire length of the stalk, but the fibers from ventral sectors remain separate until they reach the prechiasmatic region, where the ventral temporal and the ventral nasal fibers spread throughout the rostrocaudal extent of the stalk and the chiasm. The initial quadrant-specific order is completely lost at the chiasm. However, beyond the optic chiasm, the fibers are reorganized into another distinct order. In the optic tract, there is a segregation of dorsal from ventral fibers, but the nasal and temporal groups remain intermingled. The results of this study indicate that the earliest fibers in the developing optic tract are arranged according to topographical rules that differ from those obtaining behind the eye. Since all topographical order is lost between these two levels, there must be an active sorting mechanism in the region where the chiasm joins the tract. Possibly this mechanism is related to the development of the dorsoventral axis of the topographic maps in the central visual targets.

Animals↗

PubMed2003

[Arterial microcirculation in the optic chiasm, optic tracts and lateral geniculate bodies].

OBJECTIVES: The purpose of this study was to point out the microscopic vessels in the optic chiasm, optic tracts and lateral geniculate bodies. MATERIAL AND METHODS: This study was carried out on 20 brains, fixed in formaldehyde 10% and dissected under the surgical microscope. The material was summated to histological techniques on paraffin and performed on routine coloration. RESULTS: The lateral borders of the optic chiasm have more perforant branches as the median zone. The anterior and posterior segments of the optic tracts are rich in capillary vessels. The arteriolar branches penetrate into the lateral geniculate body on his inferior surface and borders. CONCLUSIONS: The knowledge of the arteriolar distribution in this segments of the optic pathways can explain the visual defects in some neuroophthalmologic syndromes.

Arterioles↗