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Show Original Contribution Physiological Correlates and Predictors of Functional Recovery After Chiasmal Decompression Noa Raz, PhD, Atira S. Bick, PhD, Alexander Klistorner, PhD, Sergey Spektor, MD, PhD, Daniel S. Reich, MD, PhD, Tamir Ben-Hur, MD, PhD, Netta Levin, MD, PhD Background: The intrinsic abilities and limits of the nervous system to repair itself after damage may be assessed using a model of optic chiasmal compression, before and after a corrective surgical procedure. Methods: Visual fields (VFs), multifocal visual evoked potentials (mfVEP), retinal nerve fiber layer (RNFL) thickness, and diffusion tensor imaging were used to evaluate a patient before and after removal of a meningioma compressing the chiasm. Normally sighted individuals served as controls. The advantage of each modality to document visual function and predict postoperative outcome (2-year follow-up) was evaluated. Results: Postsurgery visual recovery was best explained by critical mass of normally conducting fibers and not associated with average conduction amplitudes. Recovered VF was observed in quadrants in which more than 50% of fibers were identified, characterized by intact mfVEP latencies, but severely reduced amplitudes. Recovery was evident despite additional reduction of RNFL thickness and abnormal optic tract diffusivity. The critical mass of normally conducting fibers was also the best prognostic indicator for functional outcome 2 years later. Conclusions: Our results highlight the ability of the remaining normally conductive axons to predict visual recovery after decompression of the optic chiasm. The redundancy in Department of Neurology (NR, ASB, TB-H, NL), The Agnes Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem, Israel; Department of Neurosurgery (SS), Hadassah Hebrew University Medical Center, Jerusalem, Israel; Department of Ophthalmology (AK), Sydney University, Sydney, Australia; and Translational Neuroradiology Unit (DR), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. anterior visual pathways may be explained, neuroanatomically, by overlapping receptive fields. Journal of Neuro-Ophthalmology 2015;35:348-352 doi: 10.1097/WNO.0000000000000266 © 2015 by North American Neuro-Ophthalmology Society A cquired optic chiasmal abnormalities usually present with a bitemporal visual field (VF) defect. Reversibility of symptoms is often evident after a decompressive surgical procedure (1). This may serve as a suitable in vivo model for assessing the intrinsic abilities and limits of the nervous system for functional recovery after compressive damage. Although various technologies are available to assess the impact of chiasmal compression (2-6), their correlation to functional status and recovery is unclear. We evaluated a patient before and after removal of a giant meningioma compressing the entire chiasm. Multifocal visual evoked potential (mfVEP) amplitudes and latencies, retinal nerve fibers layer (RNFL) thickness measured with optic coherence tomography (OCT), and optic tract diffusivity by diffusion tensor imaging (DTI) and fiber tractography were acquired before and after craniotomy. All measurements were compared with a group of normally sighted controls. Correlation with functional status as determined with VFs was assessed for each technology. In addition, the distinctive advantage of each tool as a prognostic indicator for visual recovery was determined over 2 years after surgery. Supported in part by the Sidney and Judy Swartz fund for research in multiple sclerosis and by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, USA. METHODS The authors report no conflicts of interest. Case Report Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the full text and PDF versions of this article on the journal's Web site (www. jneuro-ophthalmology.com). Address correspondence to Netta Levin, MD, PhD, fMRI Unit, Department of Neurology, Hadassah Hebrew University Medical Center, POB 12,000, Jerusalem 91120, Israel; E-mail: netta@ hadassah.org.il 348 A 35-year-old man presented with bilateral visual loss, which he noticed 6 months before admission. Apart from VF loss, his ophthalmic examination was intact. Magnetic resonance imaging (MRI) showed a giant tuberculum sellae meningioma compressing the entire optic chiasm. No hormonal abnormalities were found. The patient underwent right fronto-orbital Raz et al: J Neuro-Ophthalmol 2015; 35: 348-352 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution craniotomy, and the tumor was completely resected. No neurological complications were reported after the surgery. Controls Seventeen normally sighted individuals aged 24.2 ± 9.1 (mean ± SD) years underwent DTI scans to obtain normal optic tracts diffusivity measurements. Six separate normally sighted controls aged 38.7 ± 13.3 underwent mfVEP to obtain normative measurements of mfVEP amplitudes and latencies in each quadrant. The study has been approved by the Hadassah Hebrew University Medical Center Ethics Committee. All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all participants. PROCEDURES Visual Fields VFs were tested using the automated perimetry (Humphrey SITA-standard 24-2 protocol with stimulus 3; Carl Zeiss Meditec, Inc, Dublin, CA). We reviewed VFs for the presence of fixation losses and false-positive and false-negative rates. The averaged threshold detected for each spot was calculated separately for the inferotemporal, inferonasal, superotemporal, and superonasal VF quadrants (the dimmer the stimuli detected, the higher the threshold number; therefore, the higher the threshold, the better the patient has performed the test). VFs were measured preoperatively, immediately after surgery, 4, 12, and 24 months later. To assess visual outcome in comparison with age-related norms, VFs obtained 2 years after surgery also were evaluated by means of total deviation. Total deviation was calculated separately for the inferotemporal, inferonasal, superotemporal, and superonasal quadrants. Multifocal Visual Evoked Potentials The mfVEP was performed using the AccuMap (ObjectiVision, software: Opera, Sydney, Australia). The stimulus consisted of a cortically scaled dartboard pattern of 58 segments (eccentricity up to 24°). Each segment contained 4 · 4 grid of black and white checks, which reversed patterns, according to a pseudorandom sequence. Recordings were obtained with 4 electrodes placed over the inion. Mean amplitudes and latencies were calculated for each of the 4 VFs quadrants. For details see Ref. (7); mfVEP was assessed before and 2 months after surgery. Optic Coherence Tomography RNFL thickness before and after surgery were recorded on different machines, time (Stratus OCT; Carl Zeiss Meditec, Dublin, CA), and spectral (Heidelberg Engineering, Carlsbad, CA) domain OCT, respectively. Recording was Raz et al: J Neuro-Ophthalmol 2015; 35: 348-352 done by a trained technician; an expert independently reviewed all scans to check for artifacts that might interfere with RNFL segmentation. OCT was assessed before and 4 months after surgery. MRI scans were acquired on a 3-T scanner (Trio; Siemens, Erlangen, German) using 12-channel standard head coil. Anatomical MRI sequences included 3D T1 images (minimum TE, flip angle 9°, TR = 2,300 ms, voxel size 1 · 1 · 1.1 mm). Diffusion Tensor Imaging DTI data were acquired using diffusion-weighted imaging sequence (single-shot, spin-echo, TE = 94 ms, TR = 7,127-8,224 ms). To cover the whole brain, 52-60 axial, 2 mm thick slices (no skip) were acquired for 2 b-values, b = 0 and b = 1,000 s/mm2. The high b-value was obtained by applying gradients along 64 different diffusion directions, including 2 averages. DTI image processing and analysis was performed using the open-source mrVista package http://vistalab.stanford.edu/software. Preprocessing included removing Eddy current distortions and subject motion. Each diffusion-weighted image was then registered to the mean of the (motion-corrected) non-diffusionweighted images using a 2-stage coarse-to-fine approach that maximized the normalized mutual information. The mean of the non-diffusion-weighted images was also automatically aligned to the T1 image using a rigid body mutual information algorithm. Fiber tractography was used to delineate the optic tracts in each patient, using the ConTrack algorithm (8), a probabilistic algorithm designed to identify the most likely pathway between 2 regions of interest (ROIs). For delineating the optic tracts in control subjects, optic chiasm ROIs were positioned on coronal reformations of T1 maps of each subject, centered on the right and left sides of the pituitary stalk; the volume of these regions were standardized to 485 mm3. Both lateral geniculate nuclei (LGNs) were defined anatomically on the axial and sagittal reformations of T1 maps, and their volumes were standardized to 895 mm3. Since the optic chiasm could not be detected in the patient's scan before surgery, preoperative b = 0 maps were registered to the postoperative T1 maps, in which ROIs were described. ConTrack was set to generate a set of 10,000 candidate pathways between the optic chiasm and the LGN ROIs. The candidate pathways were scored, and the top 10% (1,000) scores pathways were selected as the most likely pathways for connecting the chiasm to the LGN. Diffusivity measurements along the tract were resampled at 30 positions, calculating fractional anisotropy (FA) at each of these nodes. In this way, measures throughout the length of the fiber could be combined across different subjects. To avoid partial volume averaging with non-white matter (i.e., ventricles or gray matter), diffusion measurements were taken near the dense core of the fibers. Diffusion at the core was estimated by combining data from different voxels in 349 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution a weighted fashion, assigning greater weight to voxels that are close to the core of the estimated tract (9). DTI was assessed before and 4 months after surgery. RESULTS Preoperatively, bitemporal visual field loss was accompanied by major reduction in mfVEP amplitudes and prolongation of mfVEP latencies in the inferior fields, and RNFL thinning was present throughout the retina and not confined to the crossing nasal retinal fibers. There was reduced FA along the optic tracts (12 and 7 points outside the range of ±1 SD from controls' mean in the left and right sides, respectively) (Fig. 2). Postoperatively, there was significant improvement in VFs. Improvement in the left eye was seen immediately and continued in the subsequent months. In the right eye, VFs deteriorated immediately but improved by 4 months; further improvement was evident during the 2-year follow-up (Fig. 1). Improved VFs were evident despite sustained reduction of mfVEP amplitudes, extending more than 2 SD from controls' mean (and more than 4 SD from controls mean within the temporal quadrants of both eyes as well as the inferonasal quadrant of the right eye). In contrast to the reduced amplitudes, postsurgical mfVEP latencies were intact in all measurable regions; mfVEP latencies could be measured within quadrants in which more than 50% of the fibers were detected, that is, mfVEP amplitudes .0 nV. This was the case in all but the inferotemporal quadrant of the right eye (Fig. 1). Thus, the amount of conducting fibers, rather than the averaged level of conductance, correlated best with VF; function of more than 50% of fibers resulted in overall normal conduction latencies and intact VF. The amount of FIG. 1. Testing results over a 2-year period after removal of a tuberculum sellae meningioma. mfVEP, multifocal visual evoked potential. 350 Raz et al: J Neuro-Ophthalmol 2015; 35: 348-352 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution conducting fibers had also the best prognostic value for VF 2 years after surgery. Functional improvement four months postoperatively was not in line with the additional structural damage evident in the right eye RNFL thickness, possibly reflecting surgical injury (see Supplemental Digital Content, Figure E1, http://links.lww.com/WNO/A159). Although optic tract diffusivity (FA) improved, it did not reach normal levels (7 and 6 points were below controls' mean in the left and right tracts, respectively) (Fig. 2). DISCUSSION Improvement in visual fields after decompression of the optic chiasm has been reported in large cohorts of patients (10-12). Consecutive measurements suggest 2 stages of recovery that might stem from different biological mechanisms: a fast early improvement due to the resolution of conduction block and late improvement due to restoration of axonal transport, remyelination, or remodeling within the anterior visual pathways (12). Our study further highlights the resilience of the anterior visual pathways. Major loss of VF, marked reduction in mfVEP amplitude, and diffusivity along the optic tracts were not barriers to recovery. This adaptive ability also was supported by the decline in postsurgical RNFL thickness of the right eye. The presence of conducting fibers in our study was best assessed by the mfVEP technique. The simultaneous recording from multiple locations allowed detection of the number of conducting axons within subsets of the visual field, facilitating threshold detection (13). Reduction in mfVEP amplitude represented loss of anterior visual pathway fibers and thinning of RNFL indicated its irreversible nature. Visual function, reflected in VF results, could be best explained by a critical mass of remaining normally conducting fibers. The functional improvement after surgery was probably the result of surviving fibers, as indicated by shortening of mfVEP latencies and improved diffusivity. Thus, chiasmal compression produced both permanent damage reducing the amount of fibers and reversible damage to conduction in surviving fibers. This critical mass of normally conducting fibers (mfVEP amplitude . 0 nV in more than 50% of fibers) was the best prognostic indicator for functional outcome, predicting visual performance 2 years later. The importance of a critical mass of normally conducting fibers is supported by previous studies, demonstrating that functional visual deficit (visual acuity (14) and relative afferent pupillary defect (15)) is apparent only after loss of FIG. 2. Diffusion tensor imaging and fiber tractography. Left: the optic tracts delineated in the patient preoperatively and 4 months after surgery. Right: FA values along the optic tracts in control subjects (n = 17, dark blue plots), patient before surgery (pale blue plots) and during the postsurgical period (light blue plots). Error bars represent SD. Red dotted line represents the border of the meningioma. FA, fractional anisotropy. Raz et al: J Neuro-Ophthalmol 2015; 35: 348-352 351 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution approximately 40%-50% of optic nerve axons. This threshold effect is probably related to the redundancy in the anterior visual pathways, which can be explained neuroanatomically by overlapping receptive fields. 6. 7. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: N. Raz, A. S. Bick, T. Ben-Hur, and N. Levin; b. Acquisition of data: N. Raz, S. Spektor, and N. Levin; c. Analysis and interpretation of data: N. Raz, A. S. Bick, A. Klistorner, D. Reich, T. Ben-Hur, and N. Levin. Category 2: a. Drafting the manuscript: N. Raz, A. S. Bick, D. Reich, T. Ben-Hur, and N. Levin; b. Revising it for intellectual content: N. Raz, D. Reich, T. Ben-Hur, and N. Levin. Category 3: a. Final approval of the completed manuscript: N. Raz, A. S. Bick, A. Klistorner, S. Spektor, D. Reich, T. Ben-Hur, and N. Levin. 8. 9. 10. REFERENCES 1. Foroozan R. Chiasmal syndromes. Curr Opin Ophthalmol. 2003;14:325-331. 2. Holder GE. The effects of chiasmal compression on the pattern visual evoked potential. Electroencephalogr Clin Neurophysiol. 1978;45:278-280. 3. Jayaraman M, Ambika S, Gandhi RA, Bassi SR, Ravi P, Sen P. Multifocal visual evoked potential recordings in compressive optic neuropathy secondary to pituitary adenoma. Doc Ophthalmol. 2010;121:197-204. 4. Moon CH, Hwang SC, Kim BT, Ohn YH, Park TK. Visual prognostic value of optical coherence tomography and photopic negative response in chiasmal compression. Invest Ophthalmol Vis Sci. 2011;52:8527-8533. 5. Danesh-Meyer HV, Carroll SC, Foroozan R, Savino PJ, Fan J, Jiang Y, Vander Hoorn S. Relationship between retinal nerve fiber layer and visual field sensitivity as measured by optical 352 11. 12. 13. 14. 15. coherence tomography in chiasmal compression. Invest Ophthalmol Vis Sci. 2006;47:4827-4835. Anik I, Anik Y, Koc K, Ceylan S, Genc H, Altintas O, Ozdamar D, Baykal Ceylan D. Evaluation of early visual recovery in pituitary macroadenomas after endoscopic endonasal transphenoidal surgery: quantitative assessment with diffusion tensor imaging (DTI). Acta Neurochir (Wien). 2011;153:831-842. Klistorner A, Fraser C, Garrick R, Graham S, Arvind H. Correlation between full-field and multifocal VEPs in optic neuritis. Doc Ophthalmol. 2008;116:19-27. Sherbondy AJ, Dougherty RF, Ben-Shachar M, Napel S, Wandell BA. ConTrack: finding the most likely pathways between brain regions using diffusion tractography. J Vis. 2008;15:11-16. Yeatman JD, Dougherty RF, Myall NJ, Wandell BA, Feldman HM. Tract profiles of white matter properties: automating fiber-tract quantification. PLoS One. 2012;7: e49790. Kayan A, Earl CJ. Compressive lesions of the optic nerves and chiasm. Pattern of recovery of vision following surgical treatment. Brain. 1975;98:13-28. Lennerstrand G. Visual recovery after treatment for pituitary adenoma. Acta Ophthalmol (Copenh). 1983;61:1104- 1117. Kerrison JB, Lynn MJ, Baer CA, Newman SA, Biousse V, Newman NJ. Stages of improvement in visual fields after pituitary tumor resection. Am J Ophthalmol. 2000;130:813-820. Klistorner A, Arvind H, Nguyen T, Garrick R, Paine M, Graham S, O'Day J, Griff J, Billson FS, Yiannikas C. Axonal loss and myelin in early ON loss in postacute optic neuritis. Ann Neurol. 2008;64:325-331. Frisen L, Quigley HA. Visual acuity in optic atrophy: a quantitative clinicopathological analysis. Graefes Arch Clin Exp Ophthalmol. 1984;222:71-74. Kerrison JB, Buchanan K, Rosenberg ML, Clark R, Andreason K, Alfaro DV, Grossniklaus HE, Kerrigan-Baumrind LA, Kerrigan DF, Miller NR, Quigley HA. Quantification of optic nerve axon loss associated with a relative afferent pupillary defect in the monkey. Arch Ophthalmol. 2001;119:1333-1341. Raz et al: J Neuro-Ophthalmol 2015; 35: 348-352 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |
