Prechiasmatic Optic Nerve Research Articles

MRI measurements of the normal pediatric optic nerve pathway

The purpose of this work is to establish a reference scale of optic nerve pathway measurements in pediatric patients according to age using MRI. Optic nerve pathway measurements were retrospectively analyzed using an orbits equivalent sequence on brain MRI scans of 137 pediatric patients (72 male, 65 female, average age = 7.7 years, standard deviation = 5.3). The examinations were performed on a 1.5-T or 3-T Siemens MR system using routine imaging protocols. Measurements include diameters of the orbital optic nerves (OON), prechiasmatic optic nerves (PON), optic tracts (OT), and optic chiasm (OC). Measurements were performed manually by 2 neuroradiologists, using post-processing software. Patients were stratified into five age groups for measurement analyses: (I) 0–1.49 years, (II) 1.5–2.99 years, (III) 3–5.99 years, (IV) 6–11.99 years, and (V) 12–18 years. The observed value range of OON mean diameter was 2.7 mm (Interquartile range (IQR) = 2.4–2.9), PON was 3.2 mm (IQR = 3.05–3.5), OT 2.6 mm (IQR = 2–2.9). A strong positive correlation was established between age and mean diameter of OON (r = 0.73, p < .001), PON (r = 0.59, p < .001), and OT (r = 0.72, p < .001). A significant difference in mean OON diameters was found between age groups I–II (d = 0.3, p = .01), II–III (d = 0.5, p < .001), III–IV (d = 0.5, p < .001) followed by a plateau between IV-V (d = 0.l0, p = .19). OON/OT ratio maintained a steady mean value 1 (IQR = 0.93–1.1) regardless of age (p = .7). The diameter of optic pathways was found to increase as a function of age with consistent positive correlation between nerve and tract for all ages.

In Vivo Evaluation of the Visual Pathway in Streptozotocin-Induced Diabetes by Diffusion Tensor MRI and Contrast Enhanced MRI.

Visual function has been shown to deteriorate prior to the onset of retinopathy in some diabetic patients and experimental animal models. This suggests the involvement of the brain's visual system in the early stages of diabetes. In this study, we tested this hypothesis by examining the integrity of the visual pathway in a diabetic rat model using in vivo multi-modal magnetic resonance imaging (MRI). Ten-week-old Sprague-Dawley rats were divided into an experimental diabetic group by intraperitoneal injection of 65 mg/kg streptozotocin in 0.01 M citric acid, and a sham control group by intraperitoneal injection of citric acid only. One month later, diffusion tensor MRI (DTI) was performed to examine the white matter integrity in the brain, followed by chromium-enhanced MRI of retinal integrity and manganese-enhanced MRI of anterograde manganese transport along the visual pathway. Prior to MRI experiments, the streptozotocin-induced diabetic rats showed significantly smaller weight gain and higher blood glucose level than the control rats. DTI revealed significantly lower fractional anisotropy and higher radial diffusivity in the prechiasmatic optic nerve of the diabetic rats compared to the control rats. No apparent difference was observed in the axial diffusivity of the optic nerve, the chromium enhancement in the retina, or the manganese enhancement in the lateral geniculate nucleus and superior colliculus between groups. Our results suggest that streptozotocin-induced diabetes leads to early injury in the optic nerve when no substantial change in retinal integrity or anterograde transport along the visual pathways was observed in MRI using contrast agent enhancement. DTI may be a useful tool for detecting and monitoring early pathophysiological changes in the visual system of experimental diabetes non-invasively.

Bacillus Panophthalmitis with Posterior Extension to the Prechiasmatic Optic Nerve.

A rare case of Bacillus panophthlamitis with extension to the prechiasmatic optic nerve secondary to hematogenous spreading after intravenous drug use is presented. A 27-year-old man with a recent history of trauma to the left eye presented with severe left eye pain following a binge of intravenous drug use. Visual acuity (VA) was LP. On examination he had chemosis, proptosis, elevated intraocular pressure, and a complete hyphema. CT-scan identified preseptal swelling, but no evidence of any posterior extension of the anterior process or orbital fractures. Topical and systemic therapy were initiated. On follow-up clinical examination less than 12 hours after presentation he had signs of a keratitis with worsening ophthalmoplegia and repeat imaging demonstrated posterior extension to the prechiasmatic optic nerve. Shortly after the cornea ruptured with cultures growing Bacillus. The patient underwent enucleation and has had no further progression of infection. To the best of our knowledge, this is the first report of Bacillus panophthalmitis presenting with signs of trauma with posterior extension to the prechiasmatic optic nerve.

Neuromyelitis optica phenotype associated with therapy-responsive acute peripheral neuropathy.

A 51-year-old Hispanic woman with a history of Churg-Strauss syndrome (in remission for 20 years)–associated mesangial glomerulonephritis and end-stage renal disease with a recent renal transplant and previously cured cytomegalovirus (CMV) infection who was on a tapering dose of tacrolimus presented with sudden onset of lower extremity numbness. Symptoms progressed to complete paraplegia and sensory loss over 24 hours. The following day, ascending paresis extended to bilateral upper extremities, with high thoracic sensory level and complete blindness. Initial MRI revealed contrast enhancement of bilateral prechiasmatic optic nerve as well as T2 hyperintensities involving the central gray matter of the entire spinal cord with associated edema. CSF analysis documented neutrophilic pleocytosis (182 neutrophils per mm3) and increased total protein level (142 mg/dL) without oligoclonal banding. Bacterial, fungal, and mycobacterial cultures from the CSF were negative, as was PCR for CMV, Epstein-Barr virus, herpes simplex virus, human herpesvirus 6, and varicella-zoster virus. Serologic autoimmune assessment, including onconeuronal, anti-neutrophil cytoplasmic antibody, and other rheumatologic, Lyme, and aquaporin-4 (AQP4) antibody testing, was negative. Moreover, testing for sarcoidosis and HIV antibody was unrevealing. Nerve conduction studies (NCS) performed 2 weeks after symptom onset documented severe reduction in compound motor action potential amplitudes (worse in the lower extremities), <10% slowing of distal latencies but not conduction velocities, and mildly slowed upper extremity f-wave latencies. Sensory nerve action potentials were pathologically reduced in the lower extremities (table). Needle examination (EMG) showed active, severe denervation changes in lower extremity muscles and less severe changes in upper extremity muscles. Subsequent GM1, GM2, GD1a, GD1b, and GQ1b ganglioside antibody testing was negative. The patient was diagnosed with concurrent clinically definite neuromyelitis optica (NMO) phenotype1 and acute axonal polyradiculoneuropathy with primarily axonal features.

Intracranial Leiomyosarcoma in an HIV-Infected Adult

This 33-year-old man presented with one-year history of intermittent left orbital pain and diplopia after was diagnosed as HIV infection for 6 months. He had limited movement of the left eye with impairment of nearly all gaze direction. RAPD was positive on the left. He had no weakness or sensory disturbance. MRI showed a well efined mass in the left cavernous sinus with post-gadolinium enhancement. Suprasellar extension with dural tail on the left side was noted with mild pressure effect to the left prechiasmatic optic nerve

Manganese‐enhanced MRI (MEMRI) via topical loading of Mn2+ significantly impairs mouse visual acuity: a comparison with intravitreal injection

Manganese-enhanced MRI (MEMRI) with topical loading of MnCl2 provides optic nerve enhancement comparable to that seen by intravitreal injection. However, the impact of this novel and non-invasive Mn(2+) loading method on visual function requires further assessments. The objective of this study is to determine the optimal topical Mn(2+) loading dosage for MEMRI and to assess visual function after MnCl2 loading. Intravitreal administration was performed to compare the two approaches of MnCl2 loading. Twenty-four hours after topical loading of 0, 0.5, 0.75, and 1 M MnCl2 , T1 -weighted, T2-weighted, diffusion tensor imaging and visual acuity (VA) assessments were performed to determine the best topical loading dosage for MEMRI measurements and to assess the integrity of retinas and optic nerves. Mice were perfusion fixed immediately after in vivo experiments for hematoxylin and eosin and immunohistochemistry staining. Topical loading of 1 M MnCl2 damaged the retinal photoreceptor layer with no detectable damage to retina ganglion cell layers or prechiasmatic optic nerves. For the topical loading, 0.75 M MnCl2 was required to see sufficient enhancement of the optic nerve. At this concentration the visual function was significantly affected, followed by a slow recovery. Intravitreal injection (0.25 μL of 0.2 M MnCl2 ) slightly affected VA, with full recovery a day later. To conclude, intravitreal MnCl2 injection provides more reproducible results with less adverse side-effects than topical loading.

Ataxic gait and hearing loss in a patient with a history of Mantle Cell Lymphoma

Objective: Reporting a case of Mantle Cell Lymphoma (MLC) with rapidly progressive envolvement of the central nervous system. Background: Mantle Cell Lymphoma is a B-cell malignancy, which comprises approximately 3–10% of all non-Hodgkin lymphomas with an incidence of approximately 4 to 8 cases per million people per year. It is characterized by the chromosomal translocation t(11;14)(q13;q32), which results in overexpression of the cell cycle protein cyclin D1. MCL arises in older adults (median age of 60–65 years) and has a male and caucasian predominance. Case report: JBJSM, 66 years old, female, caucasian, was referred to Internal Medicine in November 2010 for splenomegaly and thrombocytopenia. There were no complaints of fever, sweat, or loss of weight. Physical examination revealed splenomegaly and cervical lymphadenopathy. Diagnostic tests: Abdominal ultrasound: marked splenomegaly of approximately 20 cm, Upper GI: micropolyp at stomach fundus. TC Cervico Facial, thoraco-abdominal-pelvic: lymphadenopathy involving several chains: facial, axillar, mediastinal, hilar, intra-abdominal, retroperitoneal and inguinal-femoral bilaterally. Adenopathy biopsy and Immunophenotyping and immunohistochemistry studies have shown morphology compatible with replacement by non-Hodgkin lymphoma of low grade. Atypical cells expressing CD20, CD5 and cyclin D1 — histopathological diagnosis of lymphoma Mantle. The patient was treated with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) with relapse 15 months later and was again given RCHOP (6 cycles) — Last cycle in November 2012. In January of 2013, we confirmed total remission with bone biopsy and CT of the body. On February 1, 2013 the patient presented ataxic gait, paraparesis, marked asthenia and polyarthralgia most intense in the lombar spine and pelvis for 2 months and headache and tinnitus for 6 months. Physical examination: alert, ataxic gait with no preferential drop, dysmetria to the right, marked decrease in hearing acuity, cranial nerves normal, with the exception of III bilaterally. Tone maintained in the upper limbs, but hypotonia below. Muscle strenght grade V in the and II in the lower. Sensory level D6-D7. Liver and spleen not palpable. The magnetic resonance shows thickening of both trigeminal nerves, predominantly the right, and complete obliteration of the cisterns of the ganglion Gasser. Pumping of the wall of the left cavernous sinus, envolvement of the pre-chiasmatic optic nerves and the proximal portion of the acoustic nerve was also shown. In the lombar spine there was a mass extending from D12–L1 to L5–S1, circling the terminal segment of the spinal cord with consequent compression. The patient started intrathecal chemotherapy with methotrexate, cytarabine and dexamethasone 3 times per week with improved hearing loss and analytic response. On March 27, 2013, the patient initiated productive cough and asthenia and died on 10 April 2013. Discussion/conclusion: Most patients with MCL present with advanced stage disease. Approximately 75% of patients initially present with lymphadenopathy. Central nervous system involvement is rare (<5% of cases), and is usually associated with a leukemic phase. The course of MCL is moderately aggressive and variable. Median overall survival is three to four years.

P 228. Repetitive transorbital alternating current stimulation (rtACS) alpha activity enhancement in patients with visual field deficits: a prospective, randomized, blinded, controlled, multicenter study

Retrospective studies suggested that rtACS simulates neuronal activity and results in neuroplasticity ( Fedorov et al., 2011 ). Prospective, randomized, controlled studies in patients with pre-chiasmatic optic nerve damage showed that rtACS reduces visual field deficits, enhances vision-related Quality of Life ( Gall et al., 2011 ) and entrains rhythmic brain activity (Schmidt et al., 2012). This is understood to reflect periodic enforcing ( Zaehle et al., 2010 ) associated with the activation of residual vision resulting in restoration of visual field deficits ( Sabel et al., 2011 ). The objective of the present prospective multicenter study is to provide evidence that alpha power gain over occipital electrodes is a bio-marker that can predict visual field size improvement. 80 patients with pre-chiasmatic partial optic nerve damage were randomized prior to inclusion in the sham-stimulation controlled rtACS trial ( RCT ). The stimulation group (n = 44) received rtACS for 20–40 min/day on 10 consecutive days. Treatment parameters were defined daily (1) by subject specific amperage when patients have an obvious perception of phosphenes, (2) the strongest alpha frequency over occipital electrodes (lower cut-off) and (3) the flicker-fusion frequency (upper cut-off). The control group ( n = 36) received subliminal stimulation. Electroencephalographic (EEG) power spectra were assessed on each of the 10 days over the occipital cortex. The size of visual fields was measured before and after treatment with high resolution perimetry (HRP). Data analysis was non-parametric regression to account for the heterogeneous patient-population. The EEG data shows a systematic enhancement of alpha-power after stimulation ( p < .05). This effect is stronger in the treatment group as compared with the placebo group ( p < .05). Enhanced alpha-power was associated with reduced visual field deficits ( p < <.05). Clinical results are reported in a complementary abstract. The results confirm that rtACS entrains alpha-oscillatory brain activity and show that changes in brain-rhythms is associated with changes in the visual field size. Thus, EEG alpha-oscillations seem to provide a bio-marker that can predict adaptive processes in a visual system with a pre-chiasmatic lesion. Future studies should continue to address the optimization of rtACS as well as the stratification by etiology prior to clinical application in individuals or small populations. The study was co-funded by the EBS Technologies GmbH.

Imaging of the pre-chiasmatic optic nerve

Damage to the optic nerve (ON) is characterised by a reduction in visual acuity. Pre-chiasmatic lesions to the optic nerve may be of traumatic, congenital, tumoral (meningioma, glioma), inflammatory or vascular origins. In all cases, MRI is the choice means of exploration, carried out with axial and coronal sections with a thickness of 2.5-3mm and T1 and T2-weighted spin echo sequences. The coronal sections may be carried out with fat signal saturation for an elective study of the size of the retrobulbar portion of the ON.

Absent cavum with intact septum pellucidum and corpus callosum may indicate midline brain abnormalities

In a recent publication of a series of cases of absence of a visible cavum detected prenatally, Malinger et al.1 concluded that this finding is not always associated with callosal anomalies and may represent a variation of normal development with good postnatal outcome. Although this may be true in a proportion of cases, we would like to point out that absence of fluid in the cavum, with intact septum pellucidum and corpus callosum, potentially indicates subtle midline brain abnormalities that may have significant implications for perinatal management and postnatal neurological development. A 28-year-old woman presented for screening ultrasound at 19 + 4 weeks' gestation following isolated low unconjugated estriol level (0.29 multiples of the median) on serum screening for Down syndrome. Transvaginal sonography demonstrated absence of fluid within the cavum septi pellucidi but normal ventricular and callosal appearance. Follow-up ultrasound at 21 + 4 weeks confirmed these findings. Karyotyping performed on cultured amniocytes was normal. Smith–Lemli–Opitz syndrome was excluded by normal amniotic fluid 7-dehydrocholesterol level. A follow-up scan at 23 weeks showed no fluid within the cavum septi pellucidi (Figure 1). Transvaginal visualization of the corpus callosum demonstrated normal length, with possible subtle dysmorphic appearance of the splenium (Figure 2). A male infant was delivered by Cesarean section at 41 weeks after three failed inductions. Apgar scores were 3, 5 and 7 at 1, 5 and 10 min, respectively, and cord pH was 7.09. Respiratory effort was poor and he was transferred to the nursery due to mild respiratory distress. His blood glucose on arrival was < 1 mmol/L. He required two boluses of D10W and remained on D10W infusion for 48 h to achieve stabilization before discharge. He was readmitted at 11 days of age with persistent hyperbilirubinemia, low blood glucose level and weight loss. A diagnosis of cortisol deficiency, growth hormone deficiency and hypothyroidism was made, as well as, subsequently, diabetes insipidus. The adrenal insufficiency explained the prenatally detected low unconjugated estriol. Optic nerve hypoplasia was apparent on ophthalmological examination. Magnetic resonance imaging at 10 months of age showed vestigial prechiasmatic optic nerves and optic chiasm, as well as complete absence of pituitary tissue. There was posterior callosal dysgenesis. At the time of writing, he was 2 years old and was being followed for global developmental delay, hypotonia, panhypopituitarism, optic hypoplasia associated with visual impairment and symptomatic seizures. We believe that this case illustrates the need for caution in interpreting the significance of subtle midline intracranial abnormalities in the fetal brain, particularly when there is an aberration in development of the septum pellucidum. It has been well documented that visualization of the cavum septi pellucidi is a reliable means of confirming integrity of midline intracranial anatomy on screening ultrasound examination2. However, the septum pellucidum itself has not been well characterized histopathologically during fetal life, and pathogenesis in development is not well understood3. A hypothetical etiological association between septal agenesis and other midline brain anomalies has been postulated4. This is ascribed to possible vascular incidents which would explain the associated findings in embryologically disparate events. It could be extrapolated that an anomaly involving midline brain development, specifically development of the septum pellucidum, could be associated with other midline brain abnormalities. This case illustrates the importance of awareness of the possibility of pituitary and chiasmatic abnormalities, which may be difficult to detect with antenatal imaging and may result in significant clinical neonatal morbidity and developmental disability. D. Pugash*†, S. Langlois‡, P. Power§ and M. Demos¶ †Radiology, University of British Columbia, Ultrasound 1 T48, BC Women's Hospital, 4500 Oak St., Vancouver, British Columbia V6H 3 N1, Canada; ‡Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada; §Medical Genetics, British Columbia Women's Hospital, Vancouver, British Columbia, Canada; ¶Pediatrics and Neurology, University of British Columbia, Vancouver, British Columbia, Canada *Correspondence. (e-mail: dpugash@cw.bc.ca)

Monocular Vision Loss and Headache in a 60-Year-Old Liver Transplant Patient

Monocular Vision Loss and Headache in a 60-Year-Old Liver Transplant Patient

Progressive enhancement of alpha activity and visual function in patients with optic neuropathy: A two-week repeated session alternating current stimulation study

IntroductionRepetitive transorbital alternating current stimulation (rtACS) can improve visual deficits in patients with optic nerve damage. Recent retrospective results suggest that rtACS enhances oscillatory brain activity. The exact mechanisms of rtACS are unclear and little is known about possibly frequency-specific neural-plastic mechanisms. An association between bandwidth-confined neural-entrainment and vision recovery maximization could offer a novel therapeutic option for patients with optic neuropathy. ObjectivesThe goal of this prospective open-label study was to investigate if the enhancement of rhythmic brain activity over 10 days of consecutive rtACS stimulation is associated with visual field recovery. The secondary goal was to investigate neurophysiological mechanisms related to frequency dependent adaptive plasticity. Methods18 Patients with visual field impairments resulting from pre-chiasmatic partial optic nerve damage received rtACS on 10 consecutive days. Daily, subject-specific treatment parameters (<500 μA, 9–37 Hz, 25–40 min/day) were defined and EEG-spectra collected prior to and after rtACS. Visual field data was collected at day 1 and 10. The change of spectral-power in classic bandwidths were investigated and correlated with visual field deficit recovery. ResultsAfter 10 days of rtACS alpha-power over bilateral occipital electrodes was significantly larger than at baseline (FTime x alpha-powerp < 0.01). This effect was progressive over subsequent days of stimulation (cubic-fit, R2 0.70, RMSE 0.008). Perimetric results improved significantly, but they were not associated with changes in alpha-synchronization. DiscussionrtACS can induce cumulative bandwidth-confined changes in brain rhythms over multiple sessions. These findings are in line with the notion of brain-state dependent [1] and bandwidth-confined entrainment [2] as well as rtACS facilitated visual recovery [3].

Bilateral posterior RION after concomitant radiochemotherapy with temozolomide in a patient with glioblastoma multiforme: a case report

BackgroundRadiation induced optic neuropathy (RION) is a rare but severe consequence of radiation therapy that is associated with adjuvant chemotherapy, specifically therapy with vincristine or nitrosoureas. However, there is very little evidence regarding the occurrence of RION after concomitant radiochemotherapy with temozolomide.Case PresentationThe case of a 63 year old woman with glioblastoma multiforme and concomitant radiochemotherapy with temozolomide is described. Due to a slight depressive episode the patient also took hypericum perforatum. Five months after cessation of fractionated radiation and adjuvant chemotherapy with temozolomide (cumulative dose of 11040 mg) the patient developed bilateral amaurosis due to RION. Tumor regrowth was excluded by magnetic resonance imaging. After the application of gadolinium a pathognomonic contrast enhancement of both prechiasmatic optic nerves could be observed.ConclusionsIn this patient, the occurrence of RION may have been the result of radiosensitization by temozolomide, which could have been strengthened by hypericin. Consequently, physicians should avoid a concomitant application of hypericum perforatum and radiochemotherapy.

Ultrastructural characterization of the optic pathway in a mouse model of neurofibromatosis-1 optic glioma

The purpose of this study was to investigate the progression of changes in retinal ganglion cells and optic nerve glia in neurofibromatosis-1 (NF1) genetically-engineered mice with optic glioma. Optic glioma tumors were generated in Nf1+/− mice lacking Nf1 expression in GFAP+ cells (astrocytes). Standard immunohistochemistry methods were employed to identify astrocytes (GFAP, S100β), proliferating progenitor cells (sox2, nestin), microglia (Iba1), endothelial cells (CD31) and retinal ganglion cell (RGC) axons (Neurofilament 68k) in Nf1+/−, Nf1GFAPCKO (wild-type mice with Nf1 loss in glial cells), and Nf1+/−GFAPCKO (Nf1+/− mice with Nf1 loss in glial cells) mice. Ultrastructural changes in the optic chiasm and nerve were assessed by electron microscopy (EM). RGC were counted in whole retina preparations using high-resolution, mosaic confocal microscopy following their delineation by retrograde FluoroGold labeling. We found that only Nf1+/−GFAPCKO mice exhibited gross pre-chiasmatic optic nerve and chiasm enlargements containing aggregated GFAP+/nestin+ and S100β+/sox2+ cells (neoplastic glia) as well as increased numbers of blood vessels and microglia. Optic gliomas in Nf1+/−GFAPCKO mice contained axon fiber irregularities and multilamellar bodies of degenerated myelin. EM and EM tomographic analyses showed increased glial disorganization, disoriented axonal projections, profiles of degenerating myelin and structural alterations at nodes of Ranvier. Lastly, we found reduced RGC numbers in Nf1+/−GFAPCKO mice, supporting a model in which the combination of optic nerve Nf1 heterozygosity and glial cell Nf1 loss results in disrupted axonal-glial relationships, subsequently culminating in the degeneration of optic nerve axons and loss of their parent RGC neurons.

Optic nerve and chiasm enlargement in a case of infantile Krabbe disease: quantitative comparison with 26 age-matched controls

Hypertrophy of the optic nerves and optic chiasm is described in a 5-month-old boy with infantile Krabbe disease. Optic nerve and optic chiasm hypertrophy is a rarely described feature of Krabbe disease. The areas of the prechiasmatic optic nerves and optic chiasm were measured and compared with those of 26 age-matched controls. The areas of the prechiasmatic optic nerves and optic chiasm were 132% and 53% greater than normal, respectively.

Diversity in mammalian chiasmatic architecture: Ipsilateral axons are deflected at glial arches in the prechiasmatic optic nerve of the eutherian Tupaia belangeri

Permanent ipsilaterally projecting axons approach the chiasmatic midline in rodents but are confined to lateral parts of the optic chiasm in marsupials. Hence, principally different mechanisms were thought to underlie axon pathway choice in eutherian (placental) and marsupial mammals. First evidence of diversity in eutherian chiasmatic architecture came from studies in the newborn and adult tree shrew Tupaia belangeri (Jeffery et al. [1998] J. Comp. Neurol. 390:183-193). Here, as in marsupials, ipsilaterally projecting axons do not approach the midline. The present study aims to clarify how the developing tree shrew chiasm is organized, how glial cells are arranged therein, and the extent to which the tree shrew chiasm is similar to that of marsupials or other eutherians. By using routinely stained serial sections as well as immunohistochemistry with antibodies against glial fibrillary acidic protein, vimentin, and medium-molecular-weight neurofilament protein, we investigated chiasm formation from embryonic day 18 (E18) to birth (E43). From E22 onward, ipsilaterally projecting axons diverged from contralaterally projecting axons in prechiasmatic parts of the optic nerve. They made sharp turns when arriving at glial arches found at the transition from the optic nerve to the chiasm. Thus, during the ingrowth period of axons, Tupaia belangeri and marsupials have specialized glial arrays in common, which probably help to deflect ipsilaterally projecting axons to lateral parts of the chiasm. Our observations provide new evidence of diversity in eutherian chiasmatic architecture and identify Tupaia belangeri as an appropriate animal model for studies on the mechanisms underlying axon guidance in the developing chiasm of higher primates.

Characterization of NADPH-diaphorase-positive glial cells of the tench optic nerve after axotomy.

NADPH-diaphorase (ND) positive cell types were characterized throughout the optic nerve of the tench in normal conditions and after optic nerve transection with survival periods of 1, 3, 7, 14, 30, 60, 120 and 180 days. Astrocytic markers (S100 and glutamine synthetase) and the microglial marker tomato lectin were employed. In the control prechiasmatic optic nerve two types (types I and II) of ND-positive glial cells appeared. All type I cells showed S100 immunoreactivity, whereas only a subpopulation of them were positive to glutamine synthetase. Type II cells only presented S100 immunoreactivity. In the control anterior optic tract, all ND-positive glial cells (type III) presented immunolabeling to S100 and glutamine synthetase. After transection, types I and II did not show any changes in the staining patterns for the glial markers when observed. Two new types of ND-positive glial cells (types IV and V) were observed after axotomy. All type IV cells were S100-immunopositive, and a subpopulation presented glutamine synthetase immunolabeling. Only a subpopulation of type V cells showed glutamine synthetase immunostaining. The presence of type IV or V cells in the lesioned optic nerve occurred simultaneously with significant decreases or absence of type I cells. These data suggest that type I and III cells are astrocytes and type II cells are oligodendrocytes. Types IV and V cells are the result of the activation of type I cells after optic nerve section. The polymorphism observed in ND-positive cells may reflect different cell functions during degenerative and regenerative processes.

Primary Bilateral Optic Nerve Sarcoidosis

Sarcoidosis is a multisystemic granulomatous disease of unknown etiology. The nervous system is involved in 5%–15% of patients. In 1%–5% of patients, sarcoidosis affects the optic nerve in some manner. Sarcoid manifesting as an isolated tumor of the optic nerve is uncommon. We report here a 50-year-old woman with primary bilateral optic nerve sarcoidosis. She had a history of progressive, painless visual loss over a 2-month period. Her cerebral magnetic resonance imaging (MRI) scan revealed diffuse thickening and enhancement of the optic chiasm affecting the pre-chiasmatic optic nerves. Surgery was performed for histopathological diagnosis and decompression of the optic nerve. Analysis of a biopsy specimen confirmed a diagnosis of sarcoidosis, and the patient was treated successfully with corticosteroids.

Symptomatic compression of the optic nerve by the carotid artery: Clinical profile of 18 patients with 24 affected eyes identified by magnetic resonance imaging

Objective To characterize the clinical features and course of patients with magnetic resonance imaging (MRI)-defined optic nerve compression by the supraclinoid carotid artery. Design Retrospective, observational case series. Participants Eighteen patients with 24 affected eyes were identified by reviewing case records from the author’s referral-based neuro-ophthalmology practice. Predetermined inclusion and exclusion criteria were applied to potential participants. Main outcome measures The following variables were abstracted from the medical record: age, gender, presenting symptoms, past medical problems, visual acuity, color vision, visual field, pupillary reactions, optic disc appearance, other neurologic signs, and previously documented and follow-up examinations. Results There were eight women and ten men ranging in age from 28 to 86 years (median age, 72 years) at the time of diagnosis. Ten (56%) of 18 patients had hypertension. Twelve patients had unilateral optic neuropathy, whereas 6 patients had bilateral optic neuropathy. One patient presented with subacute superior orbital fissure syndrome due to mass effect of a dolichoectatic carotid artery. Another patient had oculomotor nerve palsy with signs of aberrant regeneration due to intracavernous mass effect of a dolichoectatic carotid artery. One patient had a bitemporal hemianopia associated with bilateral compression of the immediate prechiasmatic optic nerves by dolichoectatic carotid arteries. The predominant pattern of visual field loss in most patients reflected nerve fiber bundle injury. A central scotoma or absolute central visual field loss was noted in only 6 (25%) of 24 affected eyes. Most patients demonstrated saucerlike excavation of the optic disc. Progression of visual acuity loss occurred at a relatively slow rate. Conclusions Although uncommon, intracranial compression of the optic nerve by the carotid artery should be considered in a patient with unexplained or progressive unilateral or bilateral optic neuropathy. This entity can be diagnosed using clinical skills to exclude more common causes of optic nerve injury and coronal-oriented MRI to confirm anatomic compression of the symptomatic optic nerve. Although many affected patients have excavation of the optic disc and nerve fiber bundle visual field defects, most have additional signs atypical for glaucoma, minimizing the potential for diagnostic confusion between the two disorders.

Optic nerve regeneration after intravitreal peripheral nerve implants: trajectories of axons regrowing through the optic chiasm into the optic tracts.

We have studied axon regeneration through the optic chiasm of adult rats 30 days after prechiasmatic intracranial optic nerve crush and serial intravitreal sciatic nerve grafting on day 0 and 14 post-lesion. The experiments comprised three groups of treated rats and three groups of controls. All treated animals received intravitreal grafts either into the left eye after both left sided (unilateral) and bilateral optic nerve transection, or into both eyes after bilateral optic nerve transection. Control eyes were all sham grafted on day 0 and 14 post-lesion, and the optic nerves either unlesioned, or crushed unilaterally or bilaterally. No regeneration through the chiasm was seen in any of the lesioned control optic nerves. In all experimental groups, large numbers of axons regenerated across the optic nerve lesions ipsilateral to the grafted eyes, traversed the short distal segment of the optic nerve and invaded the chiasm without deflection. Regeneration was correlated with the absence of the mesodermal components in the scar. In all cases, axon regrowth through the chiasm appeared to establish a major crossed and a minor uncrossed projection into both optic tracts, with some aberrant growth into the contralateral optic nerve. Axons preferentially regenerated within the degenerating trajectories from their own eye, through fragmented myelin and axonal debris, and reactive astrocytes, oligodendrocytes, microglia and macrophages. In bilaterally lesioned animals, no regeneration was detected in the optic nerve of the unimplanted eye. Although astrocytes became reactive and their processes proliferated, the architecture of their intrafascicular processes was little perturbed after optic nerve transection within either the distal optic nerve segment or the chiasm. The re-establishment of a comparatively normal pattern of passage through the chiasm by regenerating axons in the adult might therefore be organised by this relatively immutable scaffold of astrocyte processes. Binocular interactions between regenerating axons from both nerves (after bilateral optic nerve transection and intravitreal grafting), and between regenerating axons and the intact transchiasmatic projections from the unlesioned eye (after unilateral optic nerve lesions and after ipsilateral grafting) may not be important in establishing the divergent trajectories, since regenerating axons behave similarly in the presence and absence of an intact projection from the other eye.