Restorative Neurology and Neuroscience - Volume 26, issue 4-5

Authors: Sabel, Bernhard A.

Article Type: Research Article

Abstract: The traditional view that visual system damage is permanent has given way to a more optimistic view. Visual loss does not remain unchanged but it can recover spontaneously to some extent. Even when the period of spontaneous recovery has ended there is still additional potential for plasticity and regeneration, even months or years after the lesion. There are two fundamental approaches to harvest this plasticity potential: (i) to rescue dying cells or induce axonal regeneration of …visual system neurons through biological (pharmacological) means and (ii) to capture the residual vision capacities and improve their functions by behavioural training. Visual training can be used to activate residual visual neurons either in the blind sectors of the visual field through alternative pathways or it can be used to activate partially damaged regions in the border zone near the lesion site. Another example of post-lesion neuroplasticity is the ability of the intact visual field sectors to (spontaneously) take over functions and this is seen, for example, in macular degeneration and even in developmental disorders, such as amblyopia who benefit from training even many years beyond the critical period. Just as plasticity after brain damage is well recognized in other functional systems (motor, somatosensory), plasticity of the visual system is now gradually being recognized as a useful mechanism whereby the brain compensates for its functional loss, either spontaneously or by repetitive visual stimulation. Show more

Citation: Restorative Neurology and Neuroscience, vol. 26, no. 4-5, pp. 243-247, 2008

Authors: Rose, Karin | Schröer, Uwe | Volk, Gerd Fabian | Schlatt, Stefan | König, Simone | Feigenspan, Andreas | Thanos, Solon

Article Type: Research Article

Abstract: Injury to the mature primate and subprimate optic nerve results in irreversible impairment and loss of vision, because the retinal ganglion cells (RGCs) fail to regenerate their cut axons within the optic nerve interior. This study was performed to examine whether aging monkey RGCs retain the ability to regenerate their axons in organ culture and whether axonal regeneration is associated with specific proteomic profile. Retinal stripes obtained from marmoset eyes (C. jacchus) were cultured between the …day of birth and adult stages on different substrates like laminin-1, laminin-2, collagen, matrigel and poly-D-lysine. No neurotrophic factors were added to the medium. Axonal growth was monitored with microscopy and immunohistochemistry. Onset and rate of growth was examined with time-lapse videography. Vigorous regeneration of axons occurred from identifiable morphological types of RGCs throughout all stages of life, although the numbers of axons decreased with age. Axonal growth occurred virtually only on laminin-1. Growth correlated with re-expression of the laminin-1 receptor α6-integrin and sustained staining for GAP-43 as shown by immunohistochemistry and immunoblotting. At proteomic level, there is a maturation-dependent change in the protein immunostaining within the retina. When retinal slices of the same age were compared, regeneration-specific protein staining included calmodulin, fatty acid binding protein, alpha-crystallin, IFN-gamma, cyclin-dependent kinase inhibitor (p21), beta-hemoglobin, 60s-ribosomal protein, GAP-DH and ADP-ribosylation factor (ARF). To our knowledge these data are the first from subhuman animals to suggest that axonal regeneration of injured RGCs is correlated to expression of identifiable proteins within the retina. Show more

Citation: Restorative Neurology and Neuroscience, vol. 26, no. 4-5, pp. 249-266, 2008

Authors: Gaillard, Frédéric | Domballe, Linda

Article Type: Research Article

Abstract: During the past three decades, many studies have examined the capacity of embryonic neural grafts (dissociated cells or tissue blocks) to restore lost functions following various damages to the adult mammalian brain. Only very few focused on the visual system even if it is the optimal system to examine the potential of embryonic neural grafts in repairing point-to-point networks. Collectively, these studies show that, within limits, homologous sheets of fetal tissue grafted in the occipital cortex …of adult rodents integrate into the host visual circuitry and are physiologically active. Show more

Keywords: Embryonic cells, transplantation, adult brain, visual cortex, rodent

Citation: Restorative Neurology and Neuroscience, vol. 26, no. 4-5, pp. 267-277, 2008

Authors: Prokosch, Verena | Thanos, Solon

Article Type: Research Article

Abstract: Background: Infection with Treponema pallidum causes multiorgan manifestations including isolated optic nerve involvement at any stage of the disease. This is of particular interest for resulting in severe visual impairment, which is reversible if treated adequately. Purpose: To review clinical and diagnostic findings in patients with optic nerve affection in neurosyphilis and to focus on the visual outcome after administering adjunctive cortisone to the standard therapy regimes with penicillin G. Methods/Patients: The …review is based on a retrospective case serial of 4 patients (three males: mean age 40years, range 37–42 years; one female: mean age 62years) with optic nerve involvement in neurosyphilis treated in our hospital, and on a literature review of recent publications. Patients were treated with systemic penicillin either with or without adjunctive cortisone. The major outcome measure of therapy was improvement of visual acuity. Results: Visual outcome in our case serial showed total restoration if cortisone was also administered. The bibliographic survey, which was based on 60 patients, also revealed a better improvement of vision when antibiotic medication was combined with cortisone. Conclusions: The data show that the causal therapy of choice is undoubtedly penicillin G, with adjunctive steroids playing a crucial role in improvement of optic nerve functional outcome. Physicians should consider the use of cortisone in SON whenever clinically harmless, although prospective randomized multicenter studies are required to support this recommendation. Show more

Citation: Restorative Neurology and Neuroscience, vol. 26, no. 4-5, pp. 279-289, 2008

Authors: Stoerig, Petra

Article Type: Research Article

Abstract: The current doctrine regards fields of partial cortical blindness as permanent once a temporally restricted window for spontaneous recovery has passed. Accordingly, neuropsychological rehabilitation mainly applies compensatory procedures that train patients to make better use of their sighted field. The more ambitious goal of functional recovery depends on the survival of pathways that continue to transmit retinal information from the blind field. Although wide-spread antero- and retrograde degeneration follows lesions that destroy …or denervate the primary visual cortex and cause partial cortical blindness, several retinofugal pathways survive in cats, monkeys, and humans. In all three species, they subserve a variety of visual functions which develop and improve with practice. Post lesion plasticity is greater when the lesion occurs early in life, but changes in behavioural performance and brain responses have also been demonstrated in late lesion subjects. Although the extent of functional improvement is variable, and the most effective approaches still need to be established across cohorts, the evidence for perceptual learning in fields of cortical blindness indicates that the visual processes mediated by the surviving parts of the visual system can be harnessed to improve functional outcome. Show more

Keywords: Primary visual cortex, degeneration, post lesion plasticity, age at lesion, blindsight, perceptual learning, cortical blindness, functional recovery

Citation: Restorative Neurology and Neuroscience, vol. 26, no. 4-5, pp. 291-303, 2008

Authors: Chokron, Sylvie | Perez, Celine | Obadia, Michaël | Gaudry, Isabelle | Laloum, Laurent | Gout, Olivier

Article Type: Research Article

Abstract: Purpose: Traditionally, post-chiasmatic lesions were believed to result in complete and permanent visual loss in the topographically related areas of the visual field. However, a number of studies with monkeys, and later with humans, have demonstrated spared implicit visual functioning, referred to as 'blindsight'. The present study assessed whether training this phenomenon would induce an objective restoration of conscious vision in the blind field of hemianopic patients. Methods: For a period of 22 weeks …nine patients with unilateral occipital damage participated in several forced-choice visual tasks known to elicit blindsight: pointing to visual targets, letter recognition, visual comparison between the two hemifields, target localization, and letter identification. Before and after rehabilitation, patients were submitted to a behavioral pre- and post-test, including visual detection and letter identification as well as to automated perimetry visual field testing (Humphrey Automated 24-2 Full Threshold). Results: An objective improvement was found in the behavioral tasks for all patients at the post-test stage as well as an objective enlargement of the contralesional visual field for all except one of the nine patients. An overall decrease is seen in the number of undetected points (out of 30) on automated perimetry visual field testing after rehabilitation (F (1, 16) = 22.57; p < 0.001) for both eyes (Right Eye, RE: T = 0; z = 2.52; p < 0.05; Left Eye, LE: T = 0, z = 2.37; p < 0.05) regardless of lesion side. Conclusions: The results suggest that explicit (conscious) visual detection can be restored in the blind visual field by using implicit (unconscious) visual capacities. Results are discussed regarding visual field defect rehabilitation, blindsight, attention, and brain plasticity hypotheses. Show more

Citation: Restorative Neurology and Neuroscience, vol. 26, no. 4-5, pp. 305-320, 2008

Authors: Poggel, Dorothe A. | Mueller, Iris | Kasten, Erich | Sabel, Bernhard A.

Article Type: Research Article

Abstract: Purpose: Systematic stimulation of the visual field border in patients with visual field loss after cerebral lesions improves visual function even years after the onset of partial blindness. However, computer-based training programs like Vision Restoration Training (VRT) are not equally effective in all patients. We therefore tested which factors determine training outcome and which visual and cognitive functions are changed by VRT. Methods: Multiple outcome measures were predicted using a multifactorial regression approach. Nineteen …patients with post-geniculate visual system lesions performed six months of VRT and underwent extensive testing before and after treatment, including visual field measurements, attention functions, and subjective parameters. Results: Visual field size increased significantly during training, but a number of cognitive, especially attentional, variables also improved, as did subjective visual function. The size of areas of residual vision was the strongest predictor variable for visual field increase. Demographic and lesion-related variables had little influence on training success. Conclusions: With multivariate regression models, training outcome on different variables can be accurately predicted. Moreover, visual field increase is sufficiently predictable based on a set of variables readily available to the clinician: age of the patient, time since lesion, number of absolute perimetric defects, eccentricity of the visual field border, size of areas of residual vision, and average reaction time to perimetric stimuli. Show more

Keywords: Visual field loss, restoration of function, rehabilitation, predictor, evaluation

Citation: Restorative Neurology and Neuroscience, vol. 26, no. 4-5, pp. 321-339, 2008

Authors: Gall, Carolin | Mueller, Iris | Gudlin, Julia | Lindig, Anja | Schlueter, Dorothee | Jobke, Sandra | Franke, Gabriele H. | Sabel, Bernhard A.

Article Type: Research Article

Abstract: Purpose: The aim of the study was to examine if improvements of stimulus detection performance in visual field tests after intensive visual training of the visual field border zone in patients with visual field defects are associated with changes in self-reported vision- and health-related quality of life (QoL). Methods: We studied a clinical sample of 85 patients suffering from visual field loss after brain damage that underwent repetitive, daily light stimulation (vision restoration training, …VRT) of the visual field border and the blind visual field for up to 75 hrs (N = 16) or 150 hrs (N = 69). Stimulus detection was quantified in the central visual field with a campimetric method before and after intervention. Health-related QoL was assessed by the Health-Survey SF-36 and vision-related QoL by the 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ). Results: Both vision- and health-related QoL measures improved after VRT. Significant increases were found in 8 out of 12 NEI-VFQ and 3 out of 8 SF-36 subscales. Of the 85 participants 6% showed a decrease in stimulus detection performance, 42% showed an increase of less than 5% detected stimuli, 24% showed an increase of 5–10% detected stimuli and 28% of more than 10% detected stimuli. Changes in campimetric stimulus detection rates were related to NEI-VFQ subscales point differences general vision (3 points), difficulty with near vision activities (4 points), limitations in social functioning due to vision (4 points) and driving problems (12 points). There was no relation of visual field changes to changes in SF-36 component and subscale scores. Conclusions: The NEI-VFQ is a valuable measure of self-reported visual impairment in patients with visual field defects. Stimulation of the visual field by training may lead to improvements of vision-related QoL which were correlated with the extent of visual field enlargements. Show more

Keywords: Quality of life, visual field defect, National Eye Institute Visual Function Questionnaire (NEI-VFQ)

Citation: Restorative Neurology and Neuroscience, vol. 26, no. 4-5, pp. 341-353, 2008

Authors: Kasten, Erich | Guenther, Tobias | Sabel, Bernhard A.

Article Type: Research Article

Abstract: Purpose: When studying the efficacy of vision restoration training (VRT), near-threshold and super-threshold perimetry revealed visual field enlargements whereas the Scanning Laser Ophthalmoscope (SLO) did not. Because the SLO procedure differs in many parameters from the other perimetric tests (task difficulty, inability to reveal relative defects, inverse stimulus presentation, bright red background) the question arises which of these parameters might be responsible for such discrepancies in outcome. We have therefore simulated with …a computer-based campimetry test some of the SLO parameters and compared performance with that in standard perimetry. Methods: A 46-year old female patient was evaluated with computer-based high resolution perimetry (HRP) using detection tasks of "positive" (bright) stimuli on grey background. Performance was compared with an SLO-like task using "inverse" black target stimuli on red background. Results: Detection rate was 89% when the stimuli were positive (HRP) but dropped to 79.6% and 80.4% in the SLO-like "inverse" stimulation mode with red background, and striped red background, respectively. The number of false positives increased from 8.5 when a grey background was used, to 9.8 and 9.5 for plain red and striped red background, respectively. Reaction times were prolonged from 384 ms using a grey background to 412 ms and 391 ms using a plain red and striped red background, respectively. Thus, visual fields tested with SLO-like "inverse" stimuli showed larger scotomata and prolonged reaction time. Conclusions: Inverse stimulus detection on red background is apparently a more difficult task for hemianopic patients than standard perimetric protocols (such as those used in Tuebinger Automatic Perimetry or HRP). The difference in stimulus features might explain why VRT-induced visual field enlargements could not be observed with the SLO. Our findings also suggest that vision restoration training does not improve all aspects of vision, such as inverse, chromatic stimulus detection. Show more

Keywords: Perimetry, vision, visual field, ophthalmoloscope

Citation: Restorative Neurology and Neuroscience, vol. 26, no. 4-5, pp. 355-364, 2008

Authors: Bergsma, D.P. | Van der Wildt, G.J.

Article Type: Research Article

Abstract: Purpose: To study the quality of the visual field areas that were regained after training. In those areas, we measured some of the elementary visual properties that make up the quality of visual functioning in daily-life. This was to provide information about whether the functional visual field had been enlarged. Methods: Patients with visual field defects after a CVA were trained to detect stimuli presented in the border area of the visual field defect. …Then, in the regained areas, we measured visual acuity as a measure for spatial properties. Secondly, to assess for temporal properties we measured critical flicker frequency (CFF). Finally, we studied color vision as a third property of the regained areas. Results: Since we could not predict where restoration of visual fields would occur, we did not present pre-post comparisons. However, despite the fact that training was carried out with simple white light stimuli, we could assess acuity, CFF and color vision in the regained areas. The performance of the patients during testing of the elementary properties appeared to be almost normal when compared to control subjects and comparable to the patient's own ipsilesional visual field. Conclusions: These results support the idea that the regained visual fields that emerged after training are actually used for processing additional visual stimuli other than those used during training. Show more

Keywords: Cerebral blindness, visual quality, visual training, rehabilitation, recovery

Citation: Restorative Neurology and Neuroscience, vol. 26, no. 4-5, pp. 365-375, 2008

Authors: Werth, Reinhard

Article Type: Research Article

Abstract: This paper explores whether the child's visual system is more or less vulnerable than the adult's visual system, whether the capacity of the child's visual system to recover from cerebral blindness exceeds the capacity of the adult's, and which brain structures can mediate visual functions after damage to the geniculostriate visual system. Reports about the development of visual functions in normal and in visually-deprived children and about the recovery of visual functions after incomplete damage to …the occipital lobe, unilateral hemispherectomy, and in the absence of both cerebral hemispheres in early life, are reviewed. In addition, 2 new cases are reported. A child (patient 1) is described, who was blindfolded, but had normal visual experience for 2 hours daily between the 24 and the 30 months of age. Despite the daily visual experience, there was an elevation of the luminance difference threshold (LDT) in the periphery of the visual field. An adult patient (patient 2) showed a special mode of "blindsight" that may be present in brain damaged children but that cannot be tested in young children. This patient was always able to detect targets correctly only by "feeling" their presence without actually seeing them. After damage to the geniculostriate system, lost visual functions reappeared in more than half of the children during visual-field training. In many children, the enlargement of the visual field exceeded the enlargement that was reported in hemianopic adults during visual-field training. In rare cases, visual targets were reliably detected in both visual hemifields, even after hemispherectomy. Show more

Citation: Restorative Neurology and Neuroscience, vol. 26, no. 4-5, pp. 377-389, 2008

Authors: Schumacher, Eric H. | Jacko, Julie A. | Primo, Susan A. | Main, Keith L. | Moloney, Kevin P. | Kinzel, Erin N. | Ginn, Jimmy

Article Type: Research Article

Abstract: Purpose: Neural evidence exists for cortical reorganization in human visual cortex in response to retinal disease. Macular degeneration (MD) causes the progressive loss of central visual acuity. To cope with this, MD patients often adopt a preferred retinal location (PRL, i.e., a functional retinal area in their periphery used to fixate instead of the damaged fovea). The use of a PRL may foster cortical reorganization. Methods: We used fMRI to measure brain activity in calcarine …sulcus while visually stimulating peripheral visual regions in MD patients and age-matched control participants. Results: We found that visual stimulation of the PRL in MD patients increased brain activity in cortex normally representing central vision relative to visual stimulation of a peripheral region outside the patients' PRL and relative to stimulation in the periphery of age-matched control participants. Conclusions: These data directly link cortical reorganization in MD to behavioral adaptations adopted by MD patients. These results not only confirm that large-scale cortical reorganization of visual processing occurs in humans in response to retinal disease, but also relate this reorganization to functional changes in patient behavior. Show more

Keywords: Plasticity, cortical reorganization, functional neuroimaging, fMRI, calcarine sulcus, primary visual cortex, retinal disease

Citation: Restorative Neurology and Neuroscience, vol. 26, no. 4-5, pp. 391-402, 2008

Authors: Gudlin, Julia | Mueller, Iris | Thanos, Solon | Sabel, Bernhard A.

Article Type: Research Article

Abstract: Purpose: Several studies have shown that computer-based visual stimulation improves detection performance in brain damaged patients with post-chiasmatic lesions after stroke or trauma. Because it is not known whether visual field defects after retinal lesions can also be modified by visual stimulation we explored if visual field enlargements are possible in patients with glaucoma. Methods: Five patients with primary open angle glaucoma (POAG) performed Vision Restoration Training (VRT), a computer-based vision training …for a total of 6 months in two 3-months blocks with a 3-months training-free interval between the two training periods. Perimetric testing was performed with High Resolution Perimetry (HRP) as well as with 30° and 70° white/white (W/W) and 30° blue/yellow (B/Y) conventional automatic perimetry (Oculus Twinfield). Results: After the first 3 months of training the average detection performance significantly increased in HRP (Z = -2.023, p < 0.05) and in 30° W/W perimetry (Z = -2.023, p < 0.05), but not in B/Y perimetry (Z = -1.214, p = 0.225) or in the 70° W/W perimetry, which included more peripheral, non-trained areas (Z = -0.406, p = 0.684). Visual improvements remained stable after the training-free interval. Measured by HRP after the second VRT period 3 patients achieved an increase in the ability to detect visual stimuli, however, this improvement did not reach significance (Z = -1.826, p = 0.068). Conclusions: While a small patient sample does not permit general conclusions on visual field recovery after glaucoma, this pilot study suggests that visual field defects caused by retinal lesion may be improved by systematic vision stimulation. A larger sample, randomized clinical trial is now warranted. Show more

Keywords: Glaucoma, visual field, visual field stimulation, visual field recovery

Citation: Restorative Neurology and Neuroscience, vol. 26, no. 4-5, pp. 403-412, 2008

Authors: Polat, Uri

Article Type: Research Article

Abstract: Amblyopia is a reduction of visual functions that cannot be attributed directly to the effect of any structural abnormality of the eye or the posterior visual pathway. It is caused by abnormal binocular visual experience early in life, during the 'critical period' that prevents normal development of the visual system. It is widely accepted that therapy can only be effective during the critical period, and that it is not administered after the first decade of life. …Here we provide an overview describing a recent finding of visual abnormalities in amblyopia and propose a treatment that we developed based on this finding. Both previous and new results that are presented here clearly show the success of the structured method, targeted at the specific deficiencies in amblyopia, to improve vision in children and adults. Our results suggest that the training was successful in rejuvenating the visual system and in restoring lost development from the sensory obstacle period. It is possible that the perceptual learning method used here can be applied to other sensory and non-sensory brain modules suffering from developmental problems. Show more

Keywords: Amblyopia, plasticity, lateral interactions, treatment of amblyopia, contrast sensitivity, perceptual learning, neuroplasticity

Citation: Restorative Neurology and Neuroscience, vol. 26, no. 4-5, pp. 413-424, 2008

Authors: Mitchell, Donald E.

Article Type: Research Article

Abstract: Purpose: To review work on animal models of deprivation amblyopia that points to a special role for binocular visual input in the development of spatial vision and as a component of occlusion (patching) therapy for amblyopia. Methods: The studies reviewed employ behavioural methods to measure the effects of various early experiential manipulations on the development of the visual acuity of the two eyes. Results: Short periods of concordant binocular input, if continuous, …can offset much longer daily periods of monocular deprivation to allow the development of normal visual acuity in both eyes. It appears that the visual system does not weigh all visual input equally in terms of its ability to impact on the development of vision but instead places greater weight on concordant binocular exposure. Experimental models of patching therapy for amblyopia imposed on animals in which amblyopia had been induced by a prior period of early monocular deprivation, indicate that the benefits of patching therapy may be only temporary and decline rapidly after patching is discontinued. However, when combined with critical amounts of binocular visual input each day, the benefits of patching can be both heightened and made permanent. Conclusions: Taken together with demonstrations of retained binocular connections in the visual cortex of monocularly deprived animals, a strong argument is made for inclusion of specific training of stereoscopic vision for part of the daily periods of binocular exposure that should be incorporated as part of any patching protocol for amblyopia. Show more

Keywords: Amblyopia, visual deprivation, critical period, plasticity, visual acuity, stereopsis, binocular vision, patching

Citation: Restorative Neurology and Neuroscience, vol. 26, no. 4-5, pp. 425-434, 2008

Authors: Achtman, R.L. | Green, C.S. | Bavelier, D.

Article Type: Research Article

Abstract: Purpose: Adult brain plasticity, although possible, is often difficult to elicit. Training regimens in adults can produce specific improvements on the trained task without leading to general enhancements that would improve quality of life. This paper considers the case of playing action video games as a way to induce widespread enhancement in vision. Conclusions: We review the range of visual skills altered by action video game playing as well as the game components important in promoting …visual plasticity. Further, we discuss what these results might mean in terms of rehabilitation for different patient populations. Show more

Keywords: Video games, perceptual learning, plasticity, visual attention, rehabilitation

Citation: Restorative Neurology and Neuroscience, vol. 26, no. 4-5, pp. 435-446, 2008