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PubMed2006

Optic gliomas of the anterior visual pathway.

PURPOSE OF REVIEW: To review advances in the diagnosis and management of optic-pathway gliomas made within the past 5 years. RECENT FINDINGS: Important papers regarding optic-pathway gliomas have been published recently in the following areas: neuroimaging, natural history and how the presence of neurofibromatosis type 1 affects it, unusual presentations, visual prognosis, and treatment with fractionated stereotactic radiotherapy. SUMMARY: The diagnosis and treatment of optic-pathway gliomas has been aided greatly by a greater understanding of the natural history of these tumors and their prognosis related to the presence of neurofibromatosis type 1. Advances in magnetic resonance imaging are helping to delineate tumor extent. Newer radiation techniques that spare surrounding tissues are being used to treat optic-pathway gliomas, but chemotherapy has become the first-line treatment modality.

Glioma↗

PubMed1994

Early diagnosis of optic glioma in children with neurofibromatosis type 1.

Twenty-five asymptomatic patients with neurofibromatosis type 1 (NF 1), aged 6-21 years, underwent the following examinations: intracranial magnetic resonance testing (MRI), visual acuity testing, ophthalmoscopy, and visual field and pattern reversal visual evoked potentials (VEPs). MRI showed enlargement of one or both optic nerves in six children, with bilateral involvement in three. VEPs were normal in all these patients; two of them had abnormalities on other visual examinations, although there were no subjective visual disturbances. These results show that VEPs cannot be considered as a screening test for optic pathway lesions in children with NF 1, as previously stated, and that other types of visual function examination may be more sensitive. These data may contribute to the establishment of more precise guidelines for the evaluation and treatment of children with NF 1.

Adolescent↗

PubMed1980

Anterior optic gliomas with precocious or pseudoprecocious puberty.

5 patients with gliomas of the anterior optic pathways, histologically assessed or with strong diagnostic evidence, who developed precocious or pseudoprecocious puberty (2 cases) before the operation or after radiation treatment, are presented. Only 2 patients presented familial and/or personal evidence of neurofibromatosis. The production mechanism of these sexual changes is discussed.

Adolescent↗

PubMed2005

Cerebrospinal fluid proteomic analysis reveals dysregulation of methionine aminopeptidase-2 expression in human and mouse neurofibromatosis 1-associated glioma.

Individuals affected with the neurofibromatosis 1 (NF1) tumor predisposition syndrome are prone to the development of multiple nervous system tumors, including optic pathway gliomas (OPG). The NF1 tumor suppressor gene product, neurofibromin, functions as a Ras GTPase-activating protein, and has been proposed to regulate cell growth by inhibiting Ras activity. Recent studies from our laboratory have shown that neurofibromin also regulates the mammalian target of rapamycin activity in a Ras-dependent fashion, and that the rapamycin-mediated mammalian target of rapamycin inhibition ameliorates the Nf1-/- astrocyte growth advantage. Moreover, Nf1-deficient astrocytes exhibit increased protein translation. As part of a larger effort to identify protein markers for NF1-associated astrocytomas that could be exploited for therapeutic drug design, we did an objective proteomic analysis of the cerebrospinal fluid from genetically engineered Nf1 mice with optic glioma. One of the proteins found to be increased in the cerebrospinal fluid of OPG-bearing mice was the eukaryotic initiation factor-2alpha binding protein, methionine aminopeptidase 2 (MetAP2). In this study, we show that Nf1 mouse OPGs and NF1-associated human astrocytic tumors, but not sporadic pilocytic or other low-grade astrocytomas, specifically expressed high levels of MetAP2. In addition, we show that Nf1-deficient astrocytes overexpress MetAP2 in vitro and in vivo, and that treatment with the MetAP2 inhibitor fumagillin significantly reduces Nf1-/- astrocyte proliferation in vitro. These observations suggest that MetAP2 is regulated by neurofibromin, and that MetAP2 inhibitors could be potentially employed to treat NF1-associated tumor proliferation.

Amino Acid Sequence↗

PubMed1997

A canine encephalomyelopathy with morphological abnormalities in mitochondria.

A progressive encephalomyelopathy of insidious onset affecting a 16-month-old dog is described. Clinically, the dog was ataxic, stumbled into objects and showed mild behavioral abnormalities. Light microscopic findings included profound degeneration and astrogliosis of the optic pathways, loss of Purkinje neurons, focal bilateral and symmetrical brain stem spongiosis and diffuse neuroaxial astrogliosis with swollen and abnormally shaped nuclei. Ultrastructurally, there were giant and bizarre mitochondria within neuronal perikarya and axons as well as diffuse loosening of the cerebral and cerebellar neuropil. These neuropathological findings resemble the mitochondrial encephalomyopathies of man.

Animals↗

PubMed1979

[Neuro-ophthalmological problems: the diagnostic value of contrast sensitivity].

The evaluation of the individual contrast sensitivity function may prove useful in cases affected by lesions of the optic pathways, even when the usual neuro-ophthalmological tests (i.e. visual acuity, visual field examination) are normal. The contrast sensitivity function represents an alternative method to assess the power of spatial resolution of the visual system: in particular, it enables to measure the sensitivity at high, medium and low ranges of spatial frequencies, this being unique to such a procedure. The possible physiological mechanisms underlying the contrast sensitivity function as well as its pathological changes are reviewed.

Form Perception↗

PubMed2006

Optic glioma warranting treatment in children.

PURPOSE: To describe cases of optic pathway glioma (OPG) warranting treatment in children. METHODS: This is a retrospective review of pediatric patients treated for OPG. The clinical data and imaging studies were obtained from the medical records and radiology files of patients seen at the Pediatric Neuro-Ophthalmology Clinic at the University of Illinois, Chicago and the private office of the author (LMK). RESULTS: A total of seven cases with an age range of 3-48 months at presentation were reviewed. Three of the patients were also ultimately diagnosed with neurofibromatosis type 1. Presenting symptoms included proptosis, decreased vision, gaze deficit, and nystagmus. Four patients underwent biopsies that confirmed OPG. Six of the patients were treated with intravenous chemotherapy, with three patients requiring a second chemotherapy cycle. One patient was successfully treated with an en-bloc optic nerve excision. Two patients underwent unilateral enucleation owing to globe complications. CONCLUSION: Although benign tumours, OPG can behave very aggressively in young children. Both chemotherapy and en-bloc excision can be employed for treatment.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

Laminin modulates neuritogenesis of developing rat retinal ganglion cells through a protein kinase C-dependent pathway.

Dissociated cells from rat retinae (P2-P21) were cultured to investigate interactions between brain-derived neurotrophic factor (BDNF), various substrates (poly-L-lysine, collagen, and laminin), and protein kinases upon the neuritogenesis of retinal ganglion cells (RGCs). We found that BDNF-promoted neuritogenesis was enhanced by forskolin in RGCs from rats at P2-P21 plated on either poly-L-lysine or collagen. In contrast, in cultures with a laminin substrate, the enhancer effect of forskolin was observed only in RGCs taken from the retina of rats at P2-P6. Laminin blocked the enhancement of BDNF-induced RGCs neuritogenesis by forskolin, in RGCs from either P14 or P21, and induced a tenfold increase of protein kinase C (PKC) activity compared to poly-L-lysine. This blockade was reverted with a selective PKC inhibitor and was reproduced in poly-L-lysine cultures of P14-P21 RGCs with a PKC activator. Because axotomized RGCs need both BDNF and forskolin to regenerate, we suggest that laminin can hinder this effect by simultaneous PKC activation according to a developmentally regulated pattern. We further propose a model of interaction in the optic pathways triggered by BDNF, forskolin, and laminin that may be useful in elucidating some of the biological effects seen with regenerating axons.

Animals↗

PubMedDate not supplied

Effect of light on oxygen-induced retinopathy in the rat model. Light and OIR in the rat.

The purpose of this study was to establish whether exposure to intense lighting favors the development or aggravates experimental oxygen-induced retinopathy in the newborn rat. Five groups of Wistar rats were studied. The control group was maintained for the first 14 days of life under conditions of cyclical (12L:12D) lighting at 12 Lx in room air. Two other groups were subjected, for the same amount of time, to semi-darkness (2 Lx; 12L: 12D), one with room air and the other with supplemental 80% oxygen. The final two groups were exposed to the same room air and hyperoxic treatments under intense lighting conditions (600 Lx; 12L:12D). After the treatment period, four rats were randomly chosen from each group, sacrificed and their retinas examined under electron microscope. Marked structural changes were seen only in the photoreceptor outer segments of those rats exposed to intense light. In eighty-five of the remaining rats retinal vascular morphology was examined in retinal flat mounts after intracardiac injection of India ink. Retinopathy was observed in rats treated with hyperoxia but no significant differences could be attributed to the light conditions under which the retinopathic rats had been maintained. In the rest of the rats, axonal transport along the optical pathways was evaluated after intravitreal injection of (3H) taurine. In the two groups exposed to hyperoxia, axonal transport was altered, but less markedly in those exposed to intense lighting than in those exposed to semi-darkness. Intense illumination under conditions of normoxia favors axonal transport. Exposure to intense lighting does not seem to aggravate oxygen induced retinopathy in the rat though it does produce structural lesions of the photoreceptors.

Animals↗

PubMed2004

Complete recovery of visual functions after multimodality treatment for intrinsic chiasmatic-hypothalamic astrocytoma--case report.

A 21-year-old female was admitted with complaints of severe impairment of vision. The visual acuity was 0.02 in both eyes along with residual visual fields and central scotomas. Neuroimaging disclosed a chiasmatic-hypothalamic glioma. Surgery was performed with partial removal of the intrachiasmatic part of the intrinsic tumor. The histological diagnosis was fibrillary astrocytoma. Progressive recovery of vision began in the first week after surgery. Adjuvant treatment included one course of fractionated radiation therapy and six courses of chemotherapy. Complete recovery of visual acuity occurred after 10 months, and the visual fields were restored after an additional 6 months. Her vision has been stable during 2 years of follow up. The prognosis for recovery of vision after treatment of optic pathway gliomas mainly depends on the severity of visual loss at admission and is negatively influenced by intrinsic tumor growth, symmetrical extension, and involvement of the chiasm. Despite the presence of all these factors in the present case, multimodality management resulted in the complete recovery of visual functions. Surgery may be indicated in cases of intrinsic chiasmatic gliomas complicated by severe visual loss.

Adult↗

PubMed2001

Leaf position optimization for step-and-shoot IMRT.

PURPOSE: To describe the theoretical basis, the algorithm, and implementation of a tool that optimizes segment shapes and weights for step-and-shoot intensity-modulated radiation therapy delivered by multileaf collimators. METHODS AND MATERIALS: The tool, called SOWAT (Segment Outline and Weight Adapting Tool) is applied to a set of segments, segment weights, and corresponding dose distribution, computed by an external dose computation engine. SOWAT evaluates the effects of changing the position of each collimating leaf of each segment on an objective function, as follows. Changing a leaf position causes a change in the segment-specific dose matrix, which is calculated by a fast dose computation algorithm. A weighted sum of all segment-specific dose matrices provides the dose distribution and allows computation of the value of the objective function. Only leaf position changes that comply with the multileaf collimator constraints are evaluated. Leaf position changes that tend to decrease the value of the objective function are retained. After several possible positions have been evaluated for all collimating leaves of all segments, an external dose engine recomputes the dose distribution, based on the adapted leaf positions and weights. The plan is evaluated. If the plan is accepted, a segment sequencer is used to make the prescription files for the treatment machine. Otherwise, the user can restart SOWAT using the new set of segments, segment weights, and corresponding dose distribution. The implementation was illustrated using two example cases. The first example is a T1N0M0 supraglottic cancer case that was distributed as a multicenter planning exercise by investigators from Rotterdam, The Netherlands. The exercise involved a two-phase plan. Phase 1 involved the delivery of 46 Gy to a concave-shaped planning target volume (PTV) consisting of the primary tumor volume and the elective lymph nodal regions II-IV on both sides of the neck. Phase 2 involved a boost of 24 Gy to the primary tumor region only. SOWAT was applied to the Phase 1 plan. Parotid sparing was a planning goal. The second implementation example is an ethmoid sinus cancer case, planned with the intent of bilateral visus sparing. The median PTV prescription dose was 70 Gy with a maximum dose constraint to the optic pathway structures of 60 Gy. RESULTS: The initial set of segments, segment weights, and corresponding dose distribution were obtained, respectively, by an anatomy-based segmentation tool, a segment weight optimization tool, and a differential scatter-air ratio dose computation algorithm as external dose engine. For the supraglottic case, this resulted in a plan that proved to be comparable to the plans obtained at the other institutes by forward or inverse planning techniques. After using SOWAT, the minimum PTV dose and PTV dose homogeneity increased; the maximum dose to the spinal cord decreased from 38 Gy to 32 Gy. The left parotid mean dose decreased from 22 Gy to 19 Gy and the right parotid mean dose from 20 to 18 Gy. For the ethmoid sinus case, the target homogeneity increased by leaf position optimization, together with a better sparing of the optical tracts. CONCLUSIONS: By using SOWAT, the plans improved with respect to all plan evaluation end points. Compliance with the multileaf collimator constraints is guaranteed. The treatment delivery time remains almost unchanged, because no additional segments are created.

Humans↗

PubMed1979

Opto-chiasmatic arachnoiditis in brothers.

Six patients (3 couples of brothers) with adhesive arachnoiditis of the opto-chiasmatic cistern, surgically verified, are presented. Only one couple of brothers offered a possible family history of a similar condition in one maternal uncle. The visual damage had almost constantly a sudden onset and was predominantly of the axial type. No gross pathology, other than the arachnoiditic involvement of the chiasmal cistern and alterations of the anterior optic pathways, was found at surgery. Pneumocisternoencephalographic findings did not prove constantly reliable for a preoperative diagnosis of the condition when compared with surgical pathology. The overall results of the neurosurgical operations (exploration of the chiasm and removal of the adhesions) can be considered as favorable and this type of treatment is once again recommended as the therapy of choice without undue delay when general or local medical treatment proves of no avail after a reasonable length of time.

Adolescent↗

PubMed1986

Spatial distribution of evoked potentials in the inferior olivary nucleus by stimulation of the visual afferents in the rat.

Visual pathways (optic disc, optic nerve and pretectal regions) were electrically stimulated and evoked potentials were explored throughout the inferior olive in the anesthetized rat. Responsive areas were identified as the caudal half of the dorsal cap, nucleus beta and the most caudal region of subnucleus c of the medial accessory olive. No field potentials were identified in the rostral half of the dorsal cap, its ventrolateral outgrowth or the dorsomedial cell column. Contralateral retinal afferents were only effective all over the responsive areas.

Animals↗

PubMed2026

Understanding septo-optic dysplasia: Endocrine implications and ophthalmic consequences.

Septo-optic dysplasia (SOD) is a heterogeneous neurodevelopmental disorder classically defined by optic nerve hypoplasia, hypothalamo-pituitary dysfunction, and midline brain abnormalities, although the full triad is not consistently present. This review synthesises current evidence on the developmental, endocrine, ophthalmic, and neuroradiological dimensions of the SOD/optic nerve hypoplasia spectrum. Shared embryological origins of the optic pathways, hypothalamus, and pituitary, together with disruption of inductive signalling pathways and pathogenic variants in developmental regulators including SOX2, HESX1, SOX3, and OTX2, provide a mechanistic basis for combined ocular and pituitary phenotypes. Clinically, affected children may present with nystagmus, strabismus, visual impairment, neonatal hypoglycaemia, or evolving pituitary hormone deficiencies, and remain at risk of neurodevelopmental morbidity. Neuroradiological studies have expanded the phenotype beyond classical midline defects to include malformations of cortical development and SOD-plus presentations. Current evidence supports longitudinal endocrine surveillance, detailed ophthalmic assessment, and multidisciplinary care, including timely hormone replacement and developmental support where indicated.

developmental genetics↗

PubMed1981

[Repeat flash static perimetry according to Enoch: a simple technique for evaluating neuro-ophthalmological patients (author's transl)].

A static perimetry technique is described, which was first introduced by Enoch. The test-target is flashing and the increment threshold is recorded continuously for five minutes. In this way, using a commercially available Goldmann perimeter, it is possible to find a time-dependent decrease in sensitivity in patients with lesions of the optic pathways. No significant loss in sensitivity is found in patients with pre-disc pathologies, who show visual field deficits. This drop in sensitivity is at least of one log unit. The phenomenon is considered to be a "fatigue" in transmission of visual information and is presumably due to lesions in the conduction system (myelin). The test, which is easily performable, can be used follow-up the lesion: when this resolves, the decrease in sensitivity also disappears. Two patients with retro-bulbar neuritis with the typical characteristics of the above mention phenomenon are presented.

Adult↗

PubMed2000

Masimo signal extraction pulse oximetry.

OBJECTIVE: To describe a new pulse oximetry technology and measurement paradigm developed by Masimo Corporation. INTRODUCTION: Patient motion, poor tissue perfusion, excessive ambient light, and electrosurgical unit interference reduce conventional pulse oximeter (CPO) measurement integrity. Patient motion frequently generates erroneous pulse oximetry values for saturation and pulse rate. Motion-induced measurement error is due in part to widespread implementation of a theoretical pulse oximetry model which assumes that arterial blood is the only light-absorbing pulsatile component in the optical path. METHODS: Masimo Signal Extraction Technology (SET) pulse oximetry begins with conventional red and infrared photoplethysmographic signals, and then employs a constellation of advanced techniques including radiofrequency and light-shielded optical sensors, digital signal processing, and adaptive filtration, to measure SpO2 accurately during challenging clinical conditions. In contrast to CPO which calculates O2 saturation from the ratio of transmitted pulsatile red and infrared light, Masimo SET pulse oximetry uses a new conceptual model of light absorption for pulse oximetry and employs the discrete saturation transform (DST) to isolate individual "saturation components" in the optical pathway. Typically, when the tissue under analysis is stationary, only the single saturation component produced by pulsatile arterial blood is present. In contrast, during patient motion, movement of non-arterial components (for example, venous blood) can be identified as additional saturation components (with a lower O2 saturation). When conditions of the Masimo model are met, the saturation component corresponding to the highest O2 saturation is reported by the instrument as SpO2. CONCLUSION: The technological strategies implemented in Masimo SET pulse oximetry effectively permit continuous monitoring of SpO2 during challenging clinical conditions of motion and poor tissue perfusion.

Artifacts↗

PubMedDate not supplied

Special issues in the management of gliomas in children with neurofibromatosis 1.

Neurofibromatosis 1 (NF1) is a common multisystem disorder that is frequently associated with neoplastic and non-neoplastic lesions within the central nervous system. Improvements in neuroimaging have led to increased detection of both types of lesions. Focal areas of increased T2 signal represent the most common abnormalities detected. The vast majority of such lesions are non-neoplastic and fluctuate in number and size during childhood. Optic pathway tumors are second in frequency and generally manifest an indolent natural history, although some lesions will increase in size over time and lead to progressive visual impairment. A smaller percentage of patients will develop gliomas within the cerebral and cerebellar hemispheres of brain-stem. This article will review areas of controversy in the evaluation and follow-up of patients with NF1 and will present our approach to these issues. We will also discuss therapeutic considerations in these patients that take into account the unique features of the underlying disorder.

Brain Neoplasms↗

PubMed2005

[Optochiasmal cavernoma: a rare cause of unilateral visual loss].

INTRODUCTION: Optic pathways cavernomas are rare vascular hamartomas that can present either with an acute chiasmal syndrome or slowly progressive visual loss. OBSERVATION: A 29-year-old patient presented with mild unilateral visual loss of rapid onset and monocular left temporal hemianopia. MRI disclosed a heterogenous enhancing optochiasmal lesion. Work-up found no evidence for an inflammatory, infectious or tumoral disease and therefore a neurosurgical approach of the lesion allowed diagnosis of cavernoma, confirmed by pathological examination. Successful resection resulted in partial recovery of the visual field. CONCLUSION: Optochiasmal cavernomas are rare, removal can improve visual outcome.

Adult↗