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Introduction: We investigated the correlation between retinal thickness and optic tract integrity in subjects with autosomal dominant Alzheimer's disease (ADAD) causing mutations., Methods: Retinal thicknesses and diffusion tensor images (DTI) were obtained using optical coherence tomography and magnetic resonance imaging, respectively. The association between retinal thickness and DTI measures was adjusted for age, sex, retinotopy, and correlation between eyes., Results: Optic tract mean diffusivity and axial diffusivity were negatively correlated with retinotopically defined ganglion cell inner plexiform thickness (GCIPL). Fractional anisotropy was negatively correlated with retinotopically defined retinal nerve fiber layer thickness. There was no correlation between outer nuclear layer (ONL) thickness and any DTI measure., Discussion: In ADAD, GCIPL thickness is significantly associated with retinotopic optic tract DTI measures even in minimally symptomatic subjects. Similar associations were not present with ONL thickness or when ignoring retinotopy. We provide in vivo evidence for optic tract changes resulting from ganglion cell pathology in ADAD., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objective: the advent of BRAF inhibitors for preoperative treatment of craniopharyngioma has necessitated the identification of BRAFV600E status. Hence, we investigated predictors of BRAFV600E mutation in craniopharyngiomas., Methods: this retrospective study utilized data from 30 patients who were newly diagnosed with craniopharyngioma between 2011 and 2021. Magnetic resonance imaging (MRI) and computed tomography were performed within 1 week prior to surgery. Genetic analysis for BRAF mutation was performed using the Oncomine next-generation sequencing panel or Sanger sequencing. The relationship between BRAF mutation and demographic data, endocrinological function and tumour characteristics on imaging was assessed., Results: tumour tissue carried the BRAFV600E mutation in nine patients. There was no significant difference in age, sex, or presence of hormonal dysfunction amongst patients with and without the BRAFV600E mutation in the tumour. Most tumours with the BRAFV600E mutation were histologically categorized as papillary craniopharyngioma (P = 0.0005), and were solid (P = 0.0002) and supra-diaphragmatic (P = 0.0033) on MRI. BRAFV600E tumours were more frequently associated with optic tract edema than wild-type tumour s (55.6 vs. 0%, P = 0.0009) and all tumour s with optic tract edema carried the BRAFV600E mutation. Optic tract edema was not associated with tumour volume, cysts, or preoperative pituitary function., Conclusions: in craniopharyngiomas, the presence of optic tract edema can predict the presence of BRAFV600E mutation with a positive predictive value of 100%. The finding should be verified in larger prospective cohorts and multivariate regression analysis., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Purpose: Damage to the adult primary visual cortex (V1) causes vision loss in the contralateral visual hemifield, initiating a process of trans-synaptic retrograde degeneration. The present study examined functional implications of this process, asking if degeneration impacted the amount of visual recovery attainable from visual restoration training in chronic patients, and if restoration training impacted optic tract (OT) shrinkage., Methods: Magnetic resonance imaging was used to measure OT volumes bilaterally in 36 patients with unilateral occipital stroke. From OT volumes, we computed laterality indices (LI), estimating the stroke-induced OT shrinkage in each case. A subset of these chronic patients (n=14, 13±6 months poststroke) underwent an average of nearly 1 year of daily visual restoration training, which repeatedly stimulated vision in their blind field. The amount of visual field recovery was quantified using Humphrey perimetry, and post training magnetic resonance imaging was used to assess the impact of training on OT shrinkage., Results: OT LI was correlated with time since stroke: it was close to 0 (no measurable OT shrinkage) in subacute participants (<6 months poststroke) while chronic participants (>6 months poststroke) exhibited LI >0, but with significant variability. Visual training did not systematically alter LI, but chronic patients with baseline LI≈0 (no OT shrinkage) exhibited greater visual field recovery than those with LI>0., Conclusions: Unilateral OT shrinkage becomes detectable with magnetic resonance imaging by ≈7 months poststroke, albeit with significant interindividual variability. Although visual restoration training did not alter the amount of degeneration already sustained, OT shrinkage appeared to serve as a biomarker of the potential for training-induced visual recovery in chronic cortically blind patients.

Repeated mild traumatic brain injury (TBI) can cause persistent neuropathological effects and is a major risk factor for chronic traumatic encephalopathy. PUFAs (n-3 polyunsaturated fatty acids) were shown to improve acute TBI outcomes in single-injury models in most cases. In this study, we demonstrate positive effects of dietary n-3 PUFA on long-term neuropathological and functional outcome in a clinically relevant model of repeated mild TBI using the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA). Adult mice, reared on n-3 PUFA adequate (higher n-3 PUFA) or deficient (lower n-3 PUFA) diets, were given a mild CHIMERA daily for 3 consecutive days. At 2 months after injury, visual function and spatial memory were evaluated. Glia cell activation was assessed by immunostaining using antibodies of ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein, and axonal damage was examined using silver staining. Repeated CHIMERA (rCHIMERA)-induced gliosis was significantly suppressed in the optic tract, corpus callosum, and hippocampus of mice fed the n-3 PUFA adequate diet compared to the deficient diet group. Considerable axonal damage was detected in the optic tract after rCHIMERA, but the adequate diet group displayed less axonal damage compared to the deficient diet group. rCHIMERA induced a drastic reduction in N1 amplitude of the visual evoked potential in both diet groups and the a-wave amplitude of the electroretinogram in the deficient diet group. However, reduction of N1 and a-wave amplitude were less severe in the adequate diet group. The Morris water maze probe test indicated a significant decrease in the number of platform crossings in the deficient diet group compared to the adequate group. In summary, dietary n-3 PUFA can attenuate persistent glial cell activation and axonal damage and improve deficits in visual function and spatial memory after repeated mild TBI. These data support the neuroprotective potential of a higher n-3 PUFA diet in ameliorating the adverse outcome of repeated mild TBI.

Background: Repetitive mild traumatic brain injury (mTBI) can result in chronic visual dysfunction. G-protein receptor 110 (GPR110, ADGRF1) is the target receptor of N-docosahexaenoylethanolamine (synaptamide) mediating the anti-neuroinflammatory function of synaptamide. In this study, we evaluated the effect of an endogenous and a synthetic ligand of GPR110, synaptamide and (4Z,7Z,10Z,13Z,16Z,19Z)-N-(2-hydroxy-2-methylpropyl) docosa-4,7,10,13,16,19-hexaenamide (dimethylsynaptamide, A8), on the mTBI-induced long-term optic tract histopathology and visual dysfunction using Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA), a clinically relevant model of mTBI., Methods: The brain injury in wild-type (WT) and GPR110 knockout (KO) mice was induced by CHIMERA applied daily for 3 days, and GPR110 ligands were intraperitoneally injected immediately following each impact. The expression of GPR110 and proinflammatory mediator tumor necrosis factor (TNF) in the brain was measured by using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in an acute phase. Chronic inflammatory responses in the optic tract and visual dysfunction were assessed by immunostaining for Iba-1 and GFAP and visual evoked potential (VEP), respectively. The effect of GPR110 ligands in vitro was evaluated by the cyclic adenosine monophosphate (cAMP) production in primary microglia isolated from adult WT or KO mouse brains., Results: CHIMERA injury acutely upregulated the GPR110 and TNF gene level in mouse brain. Repetitive CHIMERA (rCHIMERA) increased the GFAP and Iba-1 immunostaining of glia cells and silver staining of degenerating axons in the optic tract with significant reduction of N1 amplitude of visual evoked potential at up to 3.5 months after injury. Both GPR110 ligands dose- and GPR110-dependently increased cAMP in cultured primary microglia with A8, a ligand with improved stability, being more effective than synaptamide. Intraperitoneal injection of A8 at 1 mg/kg or synaptamide at 5 mg/kg significantly reduced the acute expression of TNF mRNA in the brain and ameliorated chronic optic tract microgliosis, astrogliosis, and axonal degeneration as well as visual deficit caused by injury in WT but not in GPR110 KO mice., Conclusion: Our data demonstrate that ligand-induced activation of the GPR110/cAMP system upregulated after injury ameliorates the long-term optic tract histopathology and visual impairment caused by rCHIMERA. Based on the anti-inflammatory nature of GPR110 activation, we suggest that GPR110 ligands may have therapeutic potential for chronic visual dysfunction associated with mTBI., (© 2021. The Author(s).)

Little is known about the impairments and pathological changes in the visual system in mild brain trauma, especially repetitive mild traumatic brain injury (mTBI). The goal of this study was to examine and compare the effects of repeated head impacts on the neurodegeneration, axonal integrity, and glial activity in the optic tract (OT), as well as on neuronal preservation, glial responses, and synaptic organization in the lateral geniculate nucleus (LGN) and superior colliculus (SC), in wild-type mice and transgenic animals with overexpression of human TDP-43 mutant protein (TDP-43 G348C ) at 6 months after repeated closed head traumas. Animals were also assessed in the Barnes maze (BM) task. Neurodegeneration, axonal injury, and gliosis were detected in the OT of the injured animals of both genotypes. In the traumatized mice, myelination of surviving axons was mostly preserved, and the expression of neurofilament light chain was unaffected. Repetitive mTBI did not induce changes in the LGN and the SC, nor did it affect the performance of the BM task in the traumatized wild-type and TDP-43 transgenic mice. Differences in neuropathological and behavioral assessments between the injured wild-type and TDP-43 G348C mice were not revealed. Results of the current study suggest that repetitive mTBI was associated with chronic damage and inflammation in the OT in wild-type and TDP-43 G348C mice, which were not accompanied with behavioral problems and were not affected by the TDP-43 genotype, while the LGN and the SC remained preserved in the used experimental conditions.

The degree to which glaucoma has effects in the brain beyond the eye and the visual pathways is unclear. To clarify this, we investigated white matter microstructure (WMM) in 37 tracts of patients with glaucoma, monocular blindness, and controls. We used brainlife.io for reproducibility. White matter tracts were subdivided into seven categories ranging from those primarily involved in vision (the visual white matter) to those primarily involved in cognition and motor control. In the vision tracts, WMM was decreased as measured by fractional anisotropy in both glaucoma and monocular blind subjects compared to controls, suggesting neurodegeneration due to reduced sensory inputs. A test-retest approach was used to validate these results. The pattern of results was different in monocular blind subjects, where WMM properties increased outside the visual white matter as compared to controls. This pattern of results suggests that whereas in the monocular blind loss of visual input might promote white matter reorganization outside of the early visual system, such reorganization might be reduced or absent in glaucoma. The results provide indirect evidence that in glaucoma unknown factors might limit the reorganization as seen in other patient groups following visual loss.

In humans, carotid stenosis of 70% and above might be the cause of clinical symptoms such as transient ischemic attack and stroke. No clinical or animal studies have evaluated mild carotid occlusion, and few examined unilateral occlusion. Here, Westar rats underwent bilateral or unilateral carotid occlusion of 28-45%. Long-term effects were evaluated 9-11 months later. We conducted cognitive evaluation using spatial learning in a water maze and exploration behavior in an open field. Morphology of the brain was examined by MRI using diffusion-tensor imaging (DTI) and immunohistochemistry staining of the brain and eyes. Cognitive deficit was found in spatial memory and exploration behavior in both occluded groups. Brain and eyes histology presented severe damage in the bilateral group, compared to the unilateral one. DTI revealed an increase in mean diffusivity (MD) in the ventral thalamus and a decrease in fractional anisotropy in optic nerve and optic tract in bilateral rats, while unilateral rats showed only an increase in MD in the ventral pons. In those areas, a significant change in astrocytes, microglia, and number of apoptotic cells were found. Bilateral occlusion produced severe damage to both retinas, while unilateral occlusion produced damage mainly in the occluded side. We found that mild carotid stenosis, even in a unilateral occlusion, creates behavioral abnormalities presented by brain and eye histopathology. The results support our hypothesis that gradual formation of mild carotid stenosis along the life course leads to progressive damage that may create different degenerative diseases at a later age., (© 2019 Wiley Periodicals, Inc.)

Visual dysfunction is a common occurrence after traumatic brain injury (TBI). We investigated in this study effects of single or multiple mild TBI on visual function in mice using a closed head injury model that permits unconstrained head movement after impact. Adult mice were briefly anesthetized with isoflurane and given one or three mild TBI with the closed head injury by mechanically engineered rotational acceleration (CHIMERA) device with an interinjury interval of 24 h. Mice were then tested in the Morris water maze, visual cliff, and open field tests from day 19 to day 32 and for visual evoked potential at 5 weeks after the last injury and euthanized. Mice with multiple TBI showed impaired performance in the visible platform water maze test and had increased errors in the visual cliff test. Further, there was a graded difference in visual evoked potential, with the single injury mice showing modest reduction in N1 amplitude whereas the multiple injuries produced significant reduction compared to sham and single injury groups. The optic tract of the injured mice showed increases in glial cell immunostaining. The increase in glial fibrillary acid protein immunostaining reached statistical significance for both injured groups whereas the ionized calcium binding adaptor molecule 1 immunostaining was only significantly increased in the optic tract of repeatedly injured mice. These results indicate that multiple injuries using CHIMERA may result in visual deficits, which can affect certain behavioral performances. The change in vision may be a useful marker when monitoring repeated TBI outcome and screening for protective agents from TBI.

Chronic cerebral hypoperfusion (CCH)-induced white matter lesions (WMLs) are region-specific with the optic tract (OT) displaying the most severe damages and leading to visual-based behavioral impairment. Previously we have demonstrated that anti-high-mobility group box 1 (HMGB1) neutralizing antibody (Ab) prevents CCH-induced hippocampal damages via inhibition of neuroinflammation. Here we tested the protective role of the Ab on CCH-induced OT injuries. Rats were treated with permanent occlusion of common carotid arteries (2-VO) or a sham surgery, and then administered with PBS, anti-HMGB1 Ab, or paired control Ab. Pupillary light reflex examination, visual water maze, and tapered beam-walking were performed 28 days post-surgery to investigate the behavioral deficits. Meanwhile, WMLs were measured by Klüver-Barrera (KB) and H&E staining, and glial activation was further assessed to evaluate inflammatory responses in OT. Results revealed that anti-HMGB1 Ab ameliorated the morphological damages (grade scores, vacuoles, and thickness) in OT area and preserved visual abilities. Additionally, the increased levels of inflammatory responses and expressions of TLR4 and NF-κB p65 and phosphorylated NF-κB p65 (p-p65) in OT area were partly down-regulated after anti-HMGB1 treatment. Taken together, these findings suggested that HMGB1 neutralization could ease OT injuries and visual-guided behavioral deficits via suppressing inflammatory responses.

Purpose of Review: Optic pathway gliomas are low-grade neoplasms that affect the precortical visual pathway of children and adolescents. They can affect the optic nerve, optic chiasm, optic tracts and radiations and can either be sporadic or associated with neurofibromatosis type one. Gliomas isolated to the optic nerve (ONG) represent a subgroup of optic pathway gliomas, and their treatment remains controversial. New developments in ONG treatment have emerged in recent years, and it is necessary for clinicians to have a current understanding of available therapies., Recent Findings: The current review of the literature covers the background of and recent developments in ONG treatment, with a focus on standard chemotherapy, new molecularly targeted therapies, radiation therapy and surgical resection and debulking., Summary: Although standard chemotherapy remains the mainstay of ONG treatment, newer molecularly targeted therapies such as mitogen-activated protein kinase kinase inhibitors and bevacizumab represent a promising new treatment modality, and clinical studies are ongoing.

In a patient with an optic tract syndrome, we describe the loss of retinal nerve fiber layer and retinal microvasculature using enface and optical coherence tomography angiography image analyses.

Mild TBI is often accompanied by visual system dysfunction and injury, which is at least partly caused by microglial neuroinflammatory processes initiated by the injury. Using our focal cranial blast mouse model of closed-skull mild TBI, we evaluated the ability of the cannabinoid type-2 (CB2) receptor inverse agonist SMM-189, which biases microglia from the harmful M1 state to the beneficial M2 state, to mitigate visual system dysfunction and injury after TBI. Male C57BL/6 or Thy1-EYFP reporter mice received a closed-head blast of either 0-psi (sham) or 50-psi to the left side of the cranium. Blast mice received vehicle or 6 mg/kg SMM-189 daily beginning 2 h after blast. Sham mice received vehicle. In some mice, retina and optic nerve/tract were assessed morphologically at 3-7 days after blast, while other mice were assessed functionally by Optomotry 30 days after blast and morphologically at ≥30 days after blast. Mice sacrificed at 3-7 days were treated daily until sacrificed, while those assessed ≥30 days after blast were treated daily for 2 weeks post blast. Axon damage was evident in the left optic nerve and its continuation as the right optic tract at 3 days post blast in vehicle-treated blast mice in the form of swollen axon bulbs, and was accompanied by a significant increase in the abundance of microglia. Testing at 30 days post blast revealed that the contrast sensitivity function was significantly reduced in both eyes in vehicle-treated blast mice compared to vehicle-treated sham blast mice, and axon counts at ≥30 days after blast revealed a ∼10% loss in left optic nerve in vehicle-treated blast mice. Left optic nerve axon loss was highly correlated with the left eye deficit in contrast sensitivity. Immunolabeling at 30 days post blast showed a significant increase in the abundance of microglia in the retinas of both eyes and in GFAP + Müller cell processes traversing the inner plexiform layer in the left eye of vehicle-treated blast mice. SMM-189 treatment reduced axon injury and microglial abundance at 3 days, and mitigated axon loss, contrast sensitivity deficits, microglial abundance, and Müller cell GFAP upregulation at ≥30 days after blast injury. Analysis of right optic tract microglia at 3 days post blast for M1 versus M2 markers revealed that SMM-189 biased microglia toward the M2 state, with this action of SMM-189 being linked to reduced axonal injury. Taken together, our results show that focal left side cranial blast resulted in impaired contrast sensitivity and retinal pathology bilaterally and optic nerve loss ipsilaterally. The novel cannabinoid drug SMM-189 significantly mitigated the functional deficit and the associated pathologies. Our findings suggest the value of combatting visual system injury after TBI by using CB2 inverse agonists such as SMM-189, which appear to target microglia and bias them away from the pro-inflammatory M1 state, toward the protective M2 state., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: MOG antibody disease is an autoimmune disease of the central nervous system (CNS) characterized by the presence of a serological antibody against myelin oligodendrocyte glycoprotein (MOG). MRI is instrumental in distinguishing neuromyelitis optica spectrum disorder (NMOSD) from multiple sclerosis (MS), but MRI features of MOG disease appear to overlap with NMOSD and MS., Objectives: In this study we aim to characterize the radiological features of MOG antibody disease and compare the findings with those previously described., Methods: This is a retrospective study of 26 MOG positive patients. We aim to describe their brain, spinal and orbital MRI features and compare our findings with those previously reported in the literature., Results: The majority of the abnormal findings was located on orbital MRIs, with more involvement of the anterior structures and bilateral involvement of the optic nerves. Brain abnormalities were distinct from both NMOSD and MS lesions. Spinal cord was the least affected., Conclusions: This is a dedicated radiological study aiming to characterize the features of MOG antibody disease which might aid in the proper investigation of cases presenting with acquired demyelinating disorders., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Mouse models have shown that cerebral hypoperfusion causes white matter disruption and memory impairment relevant to the study of vascular cognitive impairment and dementia. The associated mechanisms include inflammation and oxidative stress are proposed to drive disruption of myelinated axons within hypoperfused white matter. The aim of this study was to determine if increased endogenous anti-oxidant and anti-inflammatory signalling in astrocytes was protective in a model of mild cerebral hypoperfusion. Transgenically altered mice overexpressing the transcription factor Nrf2 (GFAP-Nrf2) and wild type littermates were subjected to bilateral carotid artery stenosis or sham surgery. Behavioural alterations were assessed using the radial arm maze and tissue was collected for pathology and transcriptome analysis six weeks post-surgery. GFAP-Nrf2 mice showed less pronounced behavioural impairments compared to wild types following hypoperfusion, paralleled by reduced optic tract white matter disruption and astrogliosis. There was no effect of hypoperfusion on anti-oxidant gene alterations albeit the levels were increased in GFAP-Nrf2 mice. Instead, pro-inflammatory gene expression was determined to be significantly upregulated in the optic tract of hypoperfused wild type mice but differentially affected in GFAP-Nrf2 mice. In particular, complement components (C4 and C1q) were increased in wild type hypoperfused mice but expressed at levels similar to controls in hypoperfused GFAP-Nrf2 mice. This study provides evidence that overexpression of Nrf2 in astrocytes exerts beneficial effects through repression of inflammation and supports the potential use of Nrf2-activators in the amelioration of cerebrovascular-related inflammation and white matter degeneration.

Chronic cerebral hypoperfusion (CCH) has been associated with aging-related vascular dementia, including Alzheimer's disease. It can be induced by the four-vessel occlusion/internal carotid artery (4VO/ICA) model in aged rats, resulting in persistent memory deficits, white matter injury, and significant neuronal loss in the hippocampus and cerebral cortex. The phosphodiesterase type 4 inhibitor (PDE4-I) roflumilast has been reported to have pro-cognitive effects in several behavioral paradigms. The present study evaluated the effects of repeated roflumilast treatment in aged rats that were subjected to CCH. After surgery, roflumilast (0.003 and 0.01 mg/kg) was administered intraperitoneally once per day for 29 days. Memory performance was assessed in the aversive radial maze (AvRM) 7, 14, and 21 days after CCH. The effects of roflumilast on hippocampal neurodegeneration and white matter injury were investigated using Nissl and Kluver-Barrera staining, respectively. Western blot and RT-qPCR were used to explore microglial polarization using M1 (Iba-1 and iNOS) and M2 (Arginase-1) markers. Chronic cerebral hypoperfusion caused persistent memory deficits, hippocampal neurodegeneration, and vacuolization and fiber disarrangement in white matter. Repeated roflumilast treatment restored CCH-induced cognitive impairments in aged rats but in the absence of the rescue of hippocampal neurons. Attenuation of white matter injury was detected in the optic tract in aged CCH rats that were treated with roflumilast. In vitro, roflumilast increased Arg-1 gene expression in myelin-laden primary microglia. The present data suggest that roflumilast might be useful for the treatment of cognitive sequelae associated with CCH., (Copyright © 2018. Published by Elsevier Ltd.)

Background: To investigate and quantify the impact of intracranial lesions at different locations within the visual pathway on the ganglion cell layer-inner plexiform layer (GCL-IPL) complex and the retinal nerve fiber layer (RNFL)., Methods: Patients with intracranial lesions affecting the optic chiasm (Group I) or the optic tract and/or lateral geniculate nucleus (Group II) were included. All patients received kinetic visual field assessment and underwent spectral domain optical coherence tomography. Peripapillary and papillomacular bundle (PMB) RNFL and macular GCL-IPL thickness in 4 perifoveal areas were measured and compared with normal values derived from 52 age-matched healthy control subjects. Z-scores for each parameter of every patient were calculated and compared with the normative data. Z-scores less than -2.0 (e.g., -2.5) were considered as being statistically significant., Results: Twenty-two patients (Group I and II: 13 and 9, respectively) were included. Ten of 13 patients in Group I showed significant binasal GCL-IPL thinning, with associated temporal sector thinning in 8 patients. In Group II, all 9 patients showed significant reduction of the GCL-IPL corresponding to the homonymous visual field defect, but only 4 demonstrated RNFL thinning. Contralateral RNFL thinning within the PMB clinically similar to bow-tie atrophy was evident in all patients in Group II. GCL-IPL and RNFL thinning varied in severity from mild (isolated PMB RNFL thickness reduction) to severe (bilateral asymmetrical reduction of PMB RNFL associated with asymmetric, predominantly nasal reduction of GCL-IPL) in Group I., Conclusion: Clinical abnormalities in patients with visual pathway lesions are more likely to demonstrate abnormalities of GCL-IPL than global peripapillary RNFL thickness. However, PMB thickness measurement appears to be a valuable tool to detect abnormalities of the anterior visual pathways. If peripapillary RNFL measurements are performed in such patients, PMB thickness should be considered the most useful quantitative parameter.

Adult male C57BL/6J mice have previously been reported to have motor and memory deficits after experimental closed head traumatic brain injury (TBI), without associated gross pathologic damage or neuroimaging changes detectable by magnetic resonance imaging or diffusion tensor imaging protocols. The presence of neurologic deficits, however, suggests neural damage or dysfunction in these animals. Accordingly, we undertook a histologic analysis of mice after TBI. Gross pathology and histologic analysis using Nissl stain and NeuN immunohistochemistry demonstrated no obvious tissue damage or neuron loss. However, Luxol Fast Blue stain revealed myelin injury in the optic tract, while Fluoro Jade B and silver degeneration staining revealed evidence of axonal neurodegeneration in the optic tract as well as the lateral geniculate nucleus of the thalamus and superior colliculus (detectable at 7 days, but not 24 hours, after injury). Fluoro Jade B staining was not detectable in other white matter tracts, brain regions or in cell somata. In addition, there was increased GFAP staining in these optic tract, lateral geniculate, and superior colliculus 7 days post-injury, and morphologic changes in optic tract microglia that were detectable 24 hours after injury but were more prominent 7 days post-injury. Interestingly, there were no findings of degeneration or gliosis in the suprachiasmatic nucleus, which is also heavily innervated by the optic tract. Using micro-computed tomography imaging, we also found that the optic canal appears to decrease in diameter with a dorsal-ventral load on the skull, which suggests that the optic canal may be the site of injury. These results suggest that there is axonal degeneration in the optic tract and a subset of directly innervated areas, with associated neuroinflammation and astrocytosis, which develop within 7 days of injury, and also suggest that this weight drop injury may be a model for studying indirect traumatic optic neuropathy.

A 43-year-old man noted decreased vision after head trauma, with normal neuroimaging acutely. He had a left homonymous hemianopia, confirmed with hemifield visual evoked potentials, from trauma to the right optic tract. Four months after trauma, a magnetic resonance imaging of the brain showed atrophy of the right optic tract, and funduscopy revealed optic disk pallor with decreased retinal nerve fiber layer measures consistent with an optic tract syndrome., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Amblyopia is associated with a broad array of perceptual and neural abnormalities in the visual system, particularly in untreated or unsuccessfully treated populations. Traditionally, it has been believed that the neural abnormalities are confined to the visual cortex and subcortex (e.g., lateral geniculate nucleus). Here, we investigate the presence of neuroanatomical abnormalities earlier in the visual stream, in the optic nerves and tracts, of participants with two predominant forms of amblyopia., Methods: We used diffusion magnetic resonance imaging and probabilistic tractography to compare the microstructural properties of five white matter visual pathways between 15 participants with amblyopia (eight anisometropic, five strabismic, and two exhibiting both etiologies), and 13 age-matched controls., Results: Participants with amblyopia exhibited significantly smaller mean fractional anisotropy in the optic nerve and optic tract (0.26 and 0.31 vs. 0.31 and 0.36 in controls, respectively). We also found greater mean diffusivity in the optic radiation compared to controls (0.72 μm2/s vs. 0.68 μm2/s, respectively). Comparing etiologies, the abnormalities in the precortical pathways tended to be more severe in participants with anisometropic compared to strabismic amblyopia, and anisometropic participants' optic nerves, optic tracts, and optic radiations significantly differed from control participants' (all, P < 0.05)., Conclusions: The results indicate that amblyopia may be associated with microstructural abnormalities in neural networks as early as the retina, and these abnormalities may differ between amblyopic etiologies.

Hemianopia after traumatic brain injury is not infrequent and results from retro-chiasmatic lesions. Differentiating optic pathway lesions can be challenging with classic imaging. Advanced imaging techniques as an investigational tool for posttraumatic hemianopia are discussed and their pitfalls highlighted through an illustrative case study. In a patient with posttraumatic hemianopia, MRI at 8 weeks and 2 years after trauma were analyzed. Diffusion tensor imaging (DTI) and morphometric analysis of the primary visual cortex (V1) were performed. Optical coherence tomography (OCT) was performed 2 years after trauma. DTI at 8 weeks showed a decrease in fractional anisotropy (FA) of the left optic tract together with a decrease in FA in the right optic tract and optic radiation. At 2 years, an isolated decrease of the left optic tract FA values was noticed together with signs of Wallerian degeneration on classic MR imaging. OCT showed thinning of the retina congruent with the visual field deficit. While DTI abnormalities were also present in the early scan, they were more diffuse and also encompassed functionally intact structures. Results of advanced imaging techniques need to be interpreted with caution and can vary according to the timing of imaging due to Wallerian degeneration.

Diffuse axonal injury (DAI) is a hallmark of traumatic brain injury (TBI) pathology. Recently, the Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) was developed to generate an experimental model of DAI in a mouse. The characterization of DAI using diffusion tensor magnetic resonance imaging (MRI; diffusion tensor imaging, DTI) may provide a useful set of outcome measures for preclinical and clinical studies. The objective of this study was to identify the complex neurobiological underpinnings of DTI features following DAI using a comprehensive and quantitative evaluation of DTI and histopathology in the CHIMERA mouse model. A consistent neuroanatomical pattern of pathology in specific white matter tracts was identified across ex vivo DTI maps and photomicrographs of histology. These observations were confirmed by voxelwise and regional analysis of DTI maps, demonstrating reduced fractional anisotropy (FA) in distinct regions such as the optic tract. Similar regions were identified by quantitative histology and exhibited axonal damage as well as robust gliosis. Additional analysis using a machine-learning algorithm was performed to identify regions and metrics important for injury classification in a manner free from potential user bias. This analysis found that diffusion metrics were able to identify injured brains almost with the same degree of accuracy as the histology metrics. Good agreement between regions detected as abnormal by histology and MRI was also found. The findings of this work elucidate the complexity of cellular changes that give rise to imaging abnormalities and provide a comprehensive and quantitative evaluation of the relative importance of DTI and histological measures to detect brain injury.

Aneurysmal volume expansion after endovascular treatment is caused by intra-aneurysmal thrombosis in the early postembolization period. Although postembolization mass effect on cranial nerves and other adjacent structures has been previously reported, we are unaware of reports involving the anterior visual pathway. A 66-year-old woman with a 2-week history of blurred vision without headache was found to have a large, unruptured anterior communicating artery aneurysm. One month after endovascular treatment of the aneurysm with coiling and flow diversion, the patient developed decreased vision in her right eye and a left homonymous hemianopia. Magnetic resonance imaging demonstrated compression of the right optic nerve, chiasm, and edema of the right optic tract. The patient was treated with a course of high dose corticosteroids, and over the course of several weeks, her vision improved and the optic tract edema resolved. We alert clinicians to this rare but potentially reversible visual complication of endovascular treatment of intracranial aneurysms.

Background: Optic tract dysfunction may be the predominant or only clinical manifestation of an intracranial disorder including mass legion, ischemic infarct, inflammatory disease, and trauma. Documentation of the neuroimaging features of these lesions is limited to reports mostly published before the availability of MRI. This study was undertaken to document the spectrum of MRI features in patients presenting with optic tract dysfunction., Methods: A retrospective study from 2004 to 2015 at a single tertiary care neuro-ophthalmology service of 24 patients who had unilateral optic tract dysfunction defined by a homonymous hemianopia and a relative afferent pupil defect that could not be attributed to optic neuropathy or retinopathy. Two institutional neuroradiologists, who were privy to the presence of optic tract dysfunction but not to its side or cause, independently documented the MRI abnormalities on a standard data collection form and then convened for a consensus review of the imaging abnormalities with the 2 clinician authors., Results: The clinical diagnoses were 6 ischemic strokes, 5 malignant brain tumors, 5 postoperative neurosurgical cases, 4 intracranial hemorrhages, 2 traumatic brain injuries, 1 midbrain/optic tract primary demyelination, and 1 temporal lobe herpes simplex encephalitis. In their independent review, both neuroradiologists identified MRI abnormalities in 20 (83%) cases that were extrinsic to the optic tract in the neighboring temporal lobe, midbrain, thalamus, basal ganglia, or suprasellar space. In 5 of those cases, the extrinsic abnormality included features suggesting compression of the optic tract, but these compressive features were not appreciated by either neuroradiologist until the consensus conference. In 15 cases, MRI abnormalities intrinsic to the optic tract itself were eventually identified, including T2 or fluid-attenuated inversion recovery image (FLAIR) hyperintensity (9 cases) or hypointensity (1 case), thinning (6 cases), thickening (2 cases), and contrast enhancement (1 case). However, none of these intrinsic MRI abnormalities was identified during the independent review, being detected only in the consensus conference., Conclusions: Neuroradiologists aware of unilateral optic tract dysfunction but not of its side detected extrinsic (neighborhood) MRI abnormalities in most cases but did not appreciate that these extrinsic features sometimes included compression of the optic tract. MRI abnormalities intrinsic to the optic tract were entirely overlooked during independent review, being recognized only in a consensus conference with clinician authors. Neuroradiologists are more likely to detect MRI abnormalities pertinent to optic tract dysfunction once they have more complete clinical information and with higher resolution imaging, especially T1 postcontrast axial and coronal sequences and T2 or FLAIR coronal scans.

For humans and non-human primates, the alteration of the visual pathway's white matter fibers after visual deprivation has been partially explored. However, the changes in the optic tracts after the transection of the optic nerve have not been well characterized. In the current study, we attempted to investigate the differences in optic tracts between normal and unilateral optic nerve transected macaque monkeys using diffusion tensor imaging (DTI). Four healthy neonatal macaque monkeys were randomly divided into 2 groups, with 2 in each group. Group A served as a control group, and Group B underwent unilateral (right eye) optic nerve transection to produce monocular blindness. Sixteen months (Group B 16M) and thirty-two months (Group B 32M ) after optic nerve transection, diffusion tensor imaging was performed on all monkeys. Then, we compared fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in bilateral optic tracts between Group A and Group B and between Group B 16M and Group B 32M . In both Group B 16M and Group B 32M , when compared with normal monkeys in Group A, FA was decreased and MD, AD and RD were increased in the bilateral optic tracts of monkeys with monocular blindness. Furthermore, compared with Group B 16M , FA was reduced and MD, AD, RD were more obviously increased in the bilateral optic tracts of Group B 32M , and noticeable differences in MD, AD and RD were found between the left and right optic tracts in group B 32M . We believe that the results of this study would be helpful in investigation of the histological abnormalities of the integrity damage, axonal degeneration and demyelination of optic tracts in macaque monkeys with monocular blindness by DTI parameters in noninvasively and quantitatively., (Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.)

Introduction: Olfactory groove schwannomas (OGSs) are extremely rare tumours, particularly in the paediatric population., Case Report: A 13-year-old girl presented with two epileptic seizures, papilloedema and incomplete binasal quadrantanopia. Computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated a large heterogeneously enhancing tumour of the anterior skull base with a prominent dorsal pseudocyst. Interestingly, the pseudocyst embraced the right ICA bifurcation and displaced the optic tracts, optic chiasm and optic nerves and the ipsilateral basal ganglia. The patient underwent surgery via the frontolateral approach, and the tumour was completely removed. The pseudocyst was opened, and its wall was partially resected. It subsequently resolved completely. Histopathological examination yielded the rare diagnosis of schwannoma of the anterior skull base., Conclusion: Although extremely rare, olfactory groove schwannomas can be seen in paediatric patients. Our patient is the youngest ever reported with this histopathological diagnosis along with the formation of a large pseudocyst.

Cerebral small vessel disease (CSVD) is a pathological process leading to lacunar infarcts, leukoaraiosis and cerebral microbleeds. Dysfunction of the blood brain barrier (BBB) has been proposed as a mechanism in the progression cerebral small vessel disease. A rodent model commonly used to study some aspects of CSVD is bilateral common carotid artery occlusion (BCCAO) in the rat. In the present study it was determined that gait impairment, as determined by a tapered beam test, and BBB permeability increased following BCCAO. Cilostazol, a type III phosphodiesterase inhibitor, has been shown to have anti-apoptotic effects and prevent white matter vacuolation and rarefaction induced by BCCAO in rats. In this study the protective effect of cilostazol administration on the increase BBB permeability following BCCAO was determined as well as the effect on plasma levels of circulating microparticles (MPs), cerebral white matter rarefaction, glial activation and gait disturbance. The effect of cilostazol on in vitro endothelial barriers was also evaluated. Cilostazol treatment improved BBB permeability and reduced gait disturbance, visual impairment and microglial activation in optic tract following BCCAO in vivo. It also reduced the degree of cell death and the reduction in trans-endothelial electrical resistance (TEER) in artificial endothelial barriers in vitro induced by MP treatment of in vitro barriers., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Millions of mild traumatic brain injuries (TBIs) occur every year in the United States, with many people subject to multiple head injuries that can lead to chronic behavioral dysfunction. We previously reported that mild TBI induced using closed head injuries (CHI) repeated at 24h intervals produced more acute neuron death and glial reactivity than a single CHI, and increasing the length of time between injuries to 48h reduced the cumulative acute effects of repeated CHI. To determine whether repeated CHI is associated with behavioral dysfunction or persistent cellular damage, mice receiving either five CHI at 24h intervals, five CHI at 48h intervals, or five sham injuries at 24h intervals were evaluated across a 10 week period after injury. Animals with repeated CHI exhibited motor coordination and memory deficits, but not gait abnormalities when compared to sham animals. At 10wks post-injury, no notable neuron loss or glial reactivity was observed in the cortex, hippocampus, or corpus callosum. Argyrophilic axons were found in the pyramidal tract of some injured animals, but neither silver stain accumulation nor inflammatory responses in the injury groups were statistically different from the sham group in this region. However, argyrophilic axons, microgliosis and astrogliosis were significantly increased within the optic tract of injured animals. Repeated mild CHI also resulted in microgliosis and a loss of neurofilament protein 200 in the optic nerve. Lengthening the inter-injury interval from 24h to 48h did not effectively reduce these behavioral or cellular responses. These results suggest that repeated mild CHI results in persistent behavioral dysfunction and chronic pathological changes within the visual system, neither of which was significantly attenuated by lengthening the inter-injury interval from 24h to 48h.

Dextromethorphan (DM) is a non-competitive antagonist of NMDA receptors and a widely used component of cough medicine. Recently, its indication has been extended experimentally to a wide range of disorders including inflammation-mediated central nervous system disorders such as Parkinson disease (PD) and multiple sclerosis (MS). In this study, we investigate whether DM treatment has protective effects on the hippocampal neuron damage induced by bilateral occlusion of the common carotid arteries (two-vessel occlusion [2VO]), an animal model of vascular dementia (VaD). Sprague-Dawley (SD) (10 weeks of age) rats were subjected to the 2VO, and DM was injected intraperitoneally once per day for 37 days. Neuron death, glial activation, and cognitive function were assessed at 37 days after 2VO (0.2 mg/kg, i.p., "DM-0.2" and 2 mg/kg, i.p., "DM-2"). DM-2 treatment provided protection against neuronal death and glial activation in the hippocampal CA1 subfield and reduced cognitive impairment induced by 2VO in rats. The study also demonstrates that activation of the Nrf2-HO-1 pathway and upregulation of superoxide dismutase (SOD) play important roles in these effects. These results suggest that DM is effective in treating VaD and protecting against oxidative stress, which is strongly implicated in the pathogenesis of VaD. Therefore, the present study suggests that DM treatment may represent a new and promising protective strategy for treating VaD.

Objectives: This study aimed to compare the effects of environmental enrichment in nourished (on a diet containing 16% protein) and malnourished (on a diet containing 6% protein) rats during the critical period of brain development, specifically focusing on the optic nerve., Methods: By means of morphologic and morphometric assessment of the optic nerve, we analyzed the changes caused by diet and stimulation (environmental enrichment) on postnatal day 35, a time point ideal for such morphological analysis since developmental processes are considered complete at this age., Results: Malnourished animals presented low body and brain weights and high body-to-brain weight ratio compared to well-nourished rats. Furthermore, malnourished animals showed morphological changes in the optic nerve such as edema and vacuolization characterized by increased interstitial space. The malnourished-stimulated group presented lesions characteristic of early protein malnutrition but were milder than lesions exhibited by malnourished-non-stimulated group. The morphometric analysis revealed no difference in glial cell density between groups, but there was significantly higher blood vessel density in the stimulated rats, independent of their nutritional condition., Discussion: Our data indicate that protein malnutrition imposed during the critical period of brain development alters the cytoarchitecture of the optic nerve. In addition, we affirm that a 1-hour exposure to an enriched environment everyday was sufficient for tissue preservation in rats maintained on a low-protein diet. This protective effect might be related to angiogenesis, as confirmed by the increased vascular density observed in morphometric analyses.

Infrared confocal scanning laser photography of a patient with long-standing optic tract lesion revealed a homonymous hemianopic hyporeflective image contralateral to the visual field defect. Spectral domain optical coherence tomography showed thinning of the retinal nerve fiber and retinal ganglion cell layer and thickening of the inner nuclear layer (with microcystic degeneration) in the macular area, matching the infrared image. Hyporeflective image on infrared laser photography is associated with retinal degeneration secondary to anterior visual pathway disease and, when located in homonymous hemianopic retinas, may represent a new sign of an optic tract lesion.

Mechanisms of primary blast injury caused by overpressure are not fully understood. In particular, the presence and time course of neuroinflammation are unknown and so are the signatures of reactive inflammatory cells, especially the neuroprotective versus injurious roles of microglia. In general, chronic microglial activation in the injured brain suggests a pro-degenerative role for these reactive cells. In this study, we investigated the temporal dynamics of microglial activation in the brain of mice exposed to mild-moderate blast in a shock tube. Because, in our previous work, we had found that torso shielding with rigid Plexiglas attenuates traumatic axonal injury in the brain, we also evaluated neuroinflammatory microglial responses in animals with torso protection at 7 days post blast injury. Because of the prominent involvement of the visual system in blast TBI in rodents, activated microglial cells were counted in the optic tract at various time points post-injury with stereological methods. Cell counts (activated microglial cell densities) from subjects exposed to blast TBI were compared with counts from corresponding sham animals. We found that mild-moderate blast injury causes focal activation of microglia in certain white matter tracts, including the visual pathway. In the optic tract, the density of activated microglial profiles gradually intensified from 3 to 15 days post-injury and then became attenuated at 30 days. Torso protection significantly reduced microglial activation at 7 days. These findings shed light into mechanisms of primary blast neurotrauma and may suggest novel diagnostic and monitoring methods for patients. They leave open the question of whether microglial activation post blast is protective or detrimental, although response is time limited. Finally, our findings confirm the protective role of torso shielding and stress the importance of improved or optimized body gear for warfighters or other individuals at risk for blast exposure., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Degeneration of the optic pathway has been reported in various animal species including cattle. We experienced a case of bilateral optic tract degeneration characterized by severe gliosis in a Japanese black cattle without any obvious visual defects. To evaluate the significance, pathological nature and pathogenesis of the lesions, we examined the optic pathway in 60 cattle (41 Japanese black, 13 Holstein and 6 crossbreed) with or without ocular abnormalities. None of these animals had optic canal stenosis. Degenerative changes with severe gliosis in the optic pathway, which includes the optic nerve, optic chiasm and optic tract, were only observed in 8 Japanese black cattle with or without ocular abnormalities. Furthermore, strong immunoreactivity of glial fibrillary acidic protein was observed in the retinal stratum opticum and ganglion cell layer in all 5 cattle in which the optic pathway lesions could be examined. As etiological research, we also examined whether the concentrations of vitamin A and vitamin B12 or bovine viral diarrhea virus (BVDV) infection was associated with optic pathway degeneration. However, our results suggested that the observed optic pathway degeneration was probably not caused by these factors. These facts indicate the presence of optic pathway degeneration characterized by severe gliosis that has never been reported in cattle without bilateral compressive lesions in the optic pathway or bilateral severe retinal atrophy.

Background: Synaptic deficits and neuronal loss are the major pathological manifestations of Alzheimer's disease. However, the link between the early synaptic loss and subsequent neurodegeneration is not entirely clear. Cell culture studies have shown that amyloid-β (Aβ) applied to axonal terminals can cause retrograde degeneration leading to the neuronal loss, but this process has not been demonstrated in live animals., Objective: To test if Aβ applied to retinal ganglion cell axonal terminals can induce axonal damage in the optic nerve and optic tract in mice., Methods: Aβ was injected into the terminal field of the optic tract, in the left lateral geniculate nucleus of wildtype C57BL/6 mice. Following the injection, monthly diffusion tensor imaging was performed. Three months after the injection, mice underwent visual evoked potential recordings, and then sacrificed for immunohistochemical examination., Results: There were no significant changes seen with diffusion tensor imaging in the optic nerve and optic tract 3 months after the Aβ injection. The myelin and axons in these regions remained intact according to immunohistochemistry. The only significant changes observed in this study were delayed transduction and reduced amplitude of visual evoked potentials, although both Aβ and its reversed form caused similar changes., Conclusion: Despite the published in vitro studies, there was no significant axonal damage in the optic nerve and optic tract after injecting Aβ onto retinal ganglion cell axonal terminals of wildtype C57BL/6 mice.

Inducible heat shock proteins (Hsps) are upregulated in the central nervous system in response to a wide variety of injuries. Surprisingly, however, no coherent picture has emerged regarding the magnitude, duration and cellular distribution of inducible Hsps in the visual system following injury to retinal ganglion cells (RGCs). The current study sought, therefore, to achieve the following two objectives. The first aim of this study was to systematically characterise the patterns of Hsp27 and -70 expression in the retina and optic nerve in four discrete models of retinal ganglion cell (RGC) degeneration: axonal injury (ON crush), somato-dendritic injury (NMDA-induced excitotoxicity), chronic hypoperfusion (bilateral occlusion of the carotid arteris) and experimental glaucoma. The second aim was to document Hsp27 and -70 expression in the optic tract, the subcortical retinorecipient areas of the brain, and the visual cortex during Wallerian degeneration of RGC axons. Hsp27 was robustly upregulated in the retina in each injury paradigm, with the chronic models, 2VO and experimental glaucoma, displaying a more persistent Hsp27 transcriptional response than the acute models. Hsp27 expression was always associated with astrocytes and with a subset of RGCs in each of the models excluding NMDA. Hsp27 was present within astrocytes of the optic nerve/optic tract in control rats. During Wallerian degeneration, Hsp27 was upregulated in the optic nerve/optic tract and expressed de novo by astrocytes in the lateral geniculate nucleus and the stratum opticum of the superior colliculus. Conversely, the results of our study indicate Hsp70 was minimally induced in any of the models of injury, either in the retina, or in the optic nerve/optic tract, or in the subcortical, retinorecipient areas of the brain. The findings of the present study augment our understanding of the involvement of Hsp27 and Hsp70 in the response of the visual system to RGC degeneration.

Central nervous system infiltration of Waldenström's macroglobulinemia is referred to as Bing-Neel Syndrome. We describe 2 patients whose clinical presentation was due to isolated involvement of the anterior visual pathways. The mechanism of visual failure in Bing-Neel Syndrome may involve both infiltrative and autoimmune processes.

Objective: To find a safe operative corridor to the ventricular trigone avoiding injury to the optic radiations (ORs)., Methods: In 24 adult hemispheres, dimensions of the atrium, height of the OR, and the cortex-to-atrium distance were measured. Superior parietal lobule (SPL), parieto-occipital sulcus (POS), and middle temporal gyrus (MTG) traced approaches were used to measure maximum safe angles to enter the atrium without traversing the OR. A statistical algorithm was generated using these measurements to predict the height of the OR and safe angles from measurements from MR imaging of five test hemispheres. Statistically calculated angles were compared with measured angles from dissection., Results: Mean length and height of atrium, height of OR, and cortico-atrium distances were 2.07 cm, 3.36 cm, 2.53 cm, and 4.11 cm, respectively. The height of the atrium influenced the height of the OR significantly (p < 0.0001). The height of the dilated and small atrium was > 4.5 cm (> 95th percentile) and < 2 cm (< 5th percentile), respectively. For the SPL approach, the mean sagittal angle was 15.75 to 41.04 degrees; the mean coronal angle was - 17.08 to 14.92 degrees. For the POS approach, the mean sagittal angle was 51.29 to 70.1 degrees; the mean coronal angle was -8.63 to 17.22 degrees. Mean calculated height (statistically) of the OR was 0.29 mm above the mean observed height (dissection). The calculated angles and observed angles were very similar when tested for a variability of ± 2 degrees., Conclusion: The height of the normal atrium was 2.58 cm (height of atrium to height of OR ratio was 1:0.76). An operative corridor to the atrium without damaging the OR can be calculated from MR imaging of the brain., (Georg Thieme Verlag KG Stuttgart · New York.)

Background and Purpose: In patients with neuromyelitis optica (NMO), damage to extensive regions of normal-appearing WM has been observed. To investigate the possibility that microstructural alterations are present in these WM tracts, DTI and diffusion kurtosis imaging (DKI) techniques were applied and compared., Material and Methods: Thirteen patients with NMO and 13 demographically and gender-matched controls underwent MRI using a 3T MR scanner, with DTI/DKI sequence acquired jointly fitted. Parametric fractional anisotropy maps were derived from diffusion tensor (FADTI) values using b-values of 0s/mm(2) and 1000s/mm(2). Parametric fractional anisotropy maps derived from diffusion kurtosis tensor (FADKI) values were also acquired using b-values of 0, 1000, and 2000s/mm(2). Mean FADTI and FADKI values were also calculated. A ROI analysis of the genu and splenium of the corpus callosum (CC), cerebral peduncle (CP), and optic radiation (OR) was also performed. Student's t-test and corrections for multiple comparisons were used to evaluate the data obtained., Results: A significant decrease in the FADTI values obtained for NMO patients versus controls was observed for the splenium of the CC and the left OR (p<0.05). However, just a positive trend was observed for the FADKI values associated with the same WM tracts., Conclusions: To our knowledge, this is the first study to analyze WM tracts of NMO patients using DTI and DKI. These data indicate that DKI could have limitations in evaluating the WM integrity in NMO patients. Furthermore, the results obtained are consistent with the hypothesis that diffuse brain involvement characterizes NMO., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Purpose: The differential vulnerability of white matter (WM) to acute and chronic infantile hydrocephalus and the related effects of early and late reservoir treatment are unknown, but diffusion tensor imaging (DTI) could provide this information. Thus, we characterized WM integrity using DTI in a clinically relevant model., Methods: Obstructive hydrocephalus was induced in 2-week-old felines by intracisternal kaolin injection. Ventricular reservoirs were placed 1 (early) or 2 (late) weeks post-kaolin and tapped frequently based solely on neurological deficit. Hydrocephalic and age-matched control animals were sacrificed 12 weeks postreservoir. WM integrity was evaluated in the optic system, corpus callosum, and internal capsule prereservoir and every 3 weeks using DTI. Analyses were grouped as acute (<6 weeks) or chronic (≥6 weeks)., Results: In the corpus callosum during acute stages, fractional anisotropy (FA) decreased significantly with early and late reservoir placement (p = 0.0008 and 0.0008, respectively), and diffusivity increased significantly in early (axial, radial, and mean diffusivity, p = 0.0026, 0.0012, and 0.0002, respectively) and late (radial and mean diffusivity, p = 0.01 and 0.0038, respectively) groups. Chronically, the corpus callosum was thinned and not detectable by DTI. FA was significantly lower in the optic chiasm and tracts (p = 0.0496 and 0.0052, respectively) with late but not early reservoir placement. In the internal capsule, FA in both reservoir groups increased significantly with age (p < 0.05) but diffusivity remained unchanged., Conclusions: All hydrocephalic animals treated with intermittent ventricular reservoir tapping demonstrated progressive ventriculomegaly. Both reservoir groups demonstrated WM integrity loss, with the CC the most vulnerable and the optic system the most resilient.

Purpose: Optic pathway cavernous malformations (CMs) are extremely rare, accounting for less than 1 % of all intracranial CMs. We report a case of optic pathway CM mimicking optic glioma because the initial magnetic resonance (MR) images did not disclose hemorrhagic findings such as popcorn-like lesion or hemosiderin ring., Methods: A 20-year-old woman presented with subacute left visual acuity loss and visual field defect and was referred to our hospital. Initial MR imaging findings were suggestive of optic glioma. Second MR imaging demonstrated hemorrhagic findings, but the hemorrhage was considered to be intratumoral hemorrhage from left optic pilocytic astrocytoma. She underwent radiochemotherapy and intravenous administration of corticosteroids but her symptoms deteriorated. Third and fourth MR imaging revealed enlargement of the hematoma. Therefore, the radiation therapy was interrupted at a delivered dose of 16.2 Gy, and craniotomy was performed to preserve residual right visual field. The lesion was totally removed and the histological diagnosis was CM. Her right visual field was preserved, but not improved., Results: The present case and previous cases suggest that optic pathway CMs sometimes do not initially manifest with signs of hemorrhage, so CMs should be included in the differential diagnosis of optic pathway lesions., Conclusions: Histological confirmation with preparation for total resection should be considered for rapidly progressive cases even if the neuroimaging findings are compatible with optic glioma.

Purpose: Tracking the progression of low grade tumors (LGTs) is a challenging task, due to their slow growth rate and associated complex internal tumor components, such as heterogeneous enhancement, hemorrhage, and cysts. In this paper, the authors show a semiautomatic method to reliably track the volume of LGTs and the evolution of their internal components in longitudinal MRI scans., Methods: The authors' method utilizes a spatiotemporal evolution modeling of the tumor and its internal components. Tumor components gray level parameters are estimated from the follow-up scan itself, obviating temporal normalization of gray levels. The tumor delineation procedure effectively incorporates internal classification of the baseline scan in the time-series as prior data to segment and classify a series of follow-up scans. The authors applied their method to 40 MRI scans of ten patients, acquired at two different institutions. Two types of LGTs were included: Optic pathway gliomas and thalamic astrocytomas. For each scan, a "gold standard" was obtained manually by experienced radiologists. The method is evaluated versus the gold standard with three measures: gross total volume error, total surface distance, and reliability of tracking tumor components evolution., Results: Compared to the gold standard the authors' method exhibits a mean Dice similarity volumetric measure of 86.58% and a mean surface distance error of 0.25 mm. In terms of its reliability in tracking the evolution of the internal components, the method exhibits strong positive correlation with the gold standard., Conclusions: The authors' method provides accurate and repeatable delineation of the tumor and its internal components, which is essential for therapy assessment of LGTs. Reliable tracking of internal tumor components over time is novel and potentially will be useful to streamline and improve follow-up of brain tumors, with indolent growth and behavior.

Background and Purpose: Previous studies have found gray matter alterations in the cerebellum and in the visual system in both adults and adolescents with schizophrenia. The present study was conducted to investigate whether white matter tracts associated with these regions are also affected in the early stages of the disorder., Methods: Using a 1.5 Tesla magnetic resonance imaging (MRI) scanner and fiber tracking, the optic radiations and the middle cerebellar peduncles were examined in 13 adolescents with first-admission schizophrenia and 13 healthy controls matched for age, gender, school type, and handedness., Results: Patients with schizophrenia displayed significantly decreased fractional anisotropy in the optic radiations, but no differences in the middle cerebellar peduncles compared to healthy controls., Conclusions: Our findings of altered fiber integrity in the optic radiations in adolescents with schizophrenia are in line with gray matter alterations in the visual cortices previously reported in the same sample and are in accordance with other studies that found decreased fractional anisotropy in these regions. These findings support the view that the visual system plays an important role in the pathogenesis of schizophrenia and may enhance our understanding of associations between the visual cortex and symptoms of the disorder., (Copyright © 2012 by the American Society of Neuroimaging.)