Carolin Gall

Non-invasive alternating current stimulation improves vision in optic neuropathy.

PURPOSE Partial blindness after visual system damage is considered irreversible, yet the brain has residual visual capacities and considerable plasticity potential. We now applied non-invasive alternating current stimulation (ACS) to the visual system of patients with optic nerve damage with the aim to induce recovery of visual functions. METHODS In a prospective, double-blind, randomized, placebo-controlled clinical trial patients with several year old partial optic nerve lesions were treated with ACS (n = 12) or placebo-stimulation (n = 10). ACS was delivered transorbitally for 40 minutes on 10 days. Visual outcome measures and EEG were measured before and after treatment. RESULTS ACS, but not placebo, led to significant improvement of a visual field detection deficit by 69%, and also significantly improved temporal processing of visual stimuli, detection performance in static perimetry, and visual acuity. These changes were associated with alpha-band changes in the EEG power spectra. Visual improvements were stable for at least 2-months. CONCLUSIONS ACS can induce vision restoration many years after optic neuropathy. Though the mechanism is still unclear, EEG changes indicate increased synchronization in posterior brain regions. The present study provides Class Ib evidence that non-invasive transorbital ACS is well tolerated and improves visual function in optic neuropathy.

Vision- and Health-Related Quality of Life in Patients with Visual Field Loss after Postchiasmatic Lesions

PURPOSE The purpose of the study was to assess vision-related quality of life (QoL) in patients with visual field loss (VFL) after lesions of the postchiasmatic visual pathway and to investigate the influence of VFL and reduced visual acuity (VA) on vision-related QoL. METHODS In 312 patients with postchiasmatic damage, VFL was measured by automated computer campimetry, and vision-related QoL was assessed by the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ). Health-related QoL was obtained by the SF-36 Health Survey in 272 patients. In addition, 90 degrees visual fields and VA data were obtained. NEI-VFQ and SF-36 scores were compared with those of healthy subjects and poststroke, brain-injured patients in general. Multiple analyses of covariance and multiple linear regression models for QoL results were performed with VA and VFL as independent variables. RESULTS Patients with postchiasmatic lesions who had VFL had markedly lower NEI-VFQ scores than did healthy subjects and also lower SF-36 scores than did poststroke, brain-injured patients, particularly in the domain of role functioning. VFL and VA correlated significantly with vision-related but not with health-related QoL estimates when age was considered as confounding variable. Most scales of NEI-VFQ (9/12) were sensitive to differences in VFL. CONCLUSIONS VFL and VA had a coordinate influence on vision-related QoL in brain-injured patients with postchiasmatic lesions. Diminished health-related QoL was not associated with VFL and VA. Both VFL and VA should be considered when trying to explain variance of NEI-VFQ results in patients with postchiasmatic lesions of the visual pathway.

Brain functional connectivity network breakdown and restoration in blindness

Objective: To characterize brain functional connectivity in subjects with prechiasmatic visual system damage and relate functional connectivity features to extent of vision loss. Methods: In this case-control study, resting-state, eyes-closed EEG activity was recorded in patients with partial optic nerve damage (n = 15) and uninjured controls (n = 13). We analyzed power density and functional connectivity (coherence, Granger causality), the latter as (1) between-areal coupling strength and (2) individually thresholded binary graphs. Functional connectivity was then modulated by noninvasive repetitive transorbital alternating current stimulation (rtACS; 10 days, 40 minutes daily; n = 7; sham, n = 8) to study how this would affect connectivity networks and perception. Results: Patients exhibited lower spectral power (p = 0.005), decreased short- (p = 0.015) and long-range (p = 0.033) coherence, and less densely clustered coherence networks (p = 0.025) in the high-alpha frequency band (11–13 Hz). rtACS strengthened short- (p = 0.003) and long-range (p = 0.032) alpha coherence and this was correlated with improved detection abilities (r = 0.57, p = 0.035) and processing speed (r = 0.56, p = 0.049), respectively. Conclusion: Vision loss in the blind is caused not only by primary tissue damage but also by a breakdown of synchronization in brain networks. Because visual field improvements are associated with resynchronization of alpha band coherence, brain connectivity is a key component in partial blindness and in restoration of vision.

Vision-related quality of life in first stroke patients with homonymous visual field defects

BackgroundTo evaluate vision-related and health-related quality of life (VRQoL, HRQoL) in first stroke patients with homonymous visual field defects (VFD) with respect to the extent of the lesion. Since VFD occur in approximately 10% of stroke patients the main purpose of the study was to investigate the additional impact of VFD in stroke patients hypothesizing that VFD causes diminished VRQoL.MethodsIn 177 first stroke patients with persisting VFD 2.5 years after posterior-parietal lesions VRQoL was assessed by the National-Eye-Institute-Visual-Functioning-Questionnaire (NEI-VFQ) and HRQoL by the Medical-Outcome-Study Short-Form-36 Health-Survey (SF-36). Questionnaire results of VFD-patients were compared with age- and sex-matched healthy controls and with general non-selected stroke samples as published elsewhere. VFD-type and visual acuity were partially correlated with questionnaire results.ResultsCompared to healthy controls VFD-patients had lower NEI-VFQ scores except ocular pain (Z-range -11.34 to -3.35) and lower SF-36 scores except emotional role limitations (Z-range -7.21 to -3.34). VFD-patients were less impaired in SF-36 scores than general stroke patients one month post lesion (6/8 subscales) but had lower SF-36 scores compared to stroke patients six months post lesion (5/8 subscales). Visual acuity significantly correlated with NEI-VFQ scores (r-range 0.27 to 0.48) and VFD-type with SF-36 mental subscales (r-range -0.26 to -0.36).ConclusionsVFD-patients showed substantial reductions of VRQoL and HRQoL compared to healthy normals, but better HRQoL compared to stroke patients one month post lesion. VFD-patients (although their lesion age was four times higher) had significantly lower HRQoL than a general stroke population at six months post-stroke. This indicates that the stroke-related subjective level of HRQoL impairment is significantly exacerbated by VFD. While VRQoL was primarily influenced by visual acuity, mental components of HRQoL were influenced by VFD-type with larger VFD being associated with more distress.

Non-invasive alternating current stimulation induces recovery from stroke.

BACKGROUND Recovery of post-stroke deficits can be achieved by modulating neuroplasticity with non-invasive brain stimulation. To evaluate potential effects of repetitive transorbital alternating current stimulation (rtACS) on stroke recovery we carried out a randomized, drug-controlled clinical trial. METHODS Ninety-eight patients that had suffered ischemic stroke 21.4 months earlier were randomly assigned to either group D (n=30) receiving conventional drug therapy, group ACS (n=32) treated for 12 days with rtACS, or group D/ACS (n=36) receiving combined drug therapy/rtACS. Stroke severity level (SSL) was assessed by the NIH-NINDS stroke scale before and after treatment and at a 1-month follow-up to evaluate motor impairments (weakness, ataxia), sensory loss, visual field defects, and cortical deficits (aphasia, neglect). At each time point standard EEG recordings (10-20 system) were conducted. RESULTS Before therapy SSL was moderate (9.18 ± 0.78) without significant group difference (F =0.86, p=0.43). After 12 days of treatment, SSLs of groups ACS and D/ACS significantly improved by 22.5% and 25.1% over baseline, respectively, with no such change in the control group D (+3%). SSL improvements were mainly due to recovery of motor, sensory, and speech functions. After 1-month follow-up, an additional improvement of 9.7% and 9.4% was seen for the group ACS and D/ACS which led to a total change of +32.3% and +34.7% over baseline. EEG recordings revealed greater interhemispheric synchrony between both temporal lobes which were positively correlated with clinical outcome. CONCLUSIONS Non-invasive rtACS applied to post-stroke patients can modulate brain plasticity and induce recovery from neurological deficits long after the early post lesion recovery is over.

Repetitive transorbital alternating current stimulation in optic neuropathy

BACKGROUND Visual field defects after optic nerve damage typically show a limited capacity for spontaneous and treatment-induced recovery. OBJECTIVE Repetitive transorbital alternating current stimulation (rtACS) was applied to the damaged optic nerve to evaluate visual functions after stimulation. METHODS A 27-years-old male patient suffering left optic nerve atrophy with nearly complete loss of vision 11 years after atypical traumatic damage was treated transorbitally with biphasic 10-15 pulse trains of rtACS (10-30 Hz, < 600 μA, 30-40 min daily for 10 days) which produced phosphenes. RESULTS After rtACS treatment detection ability of super-threshold stimuli increased from 3.44% to 17.75% and mean perimetric threshold from 0 dB to 2.21 dB at final diagnostics. CONCLUSION This improvement of vision may be due to increased neuronal synchronization, possibly involving strengthening of synaptic transmission along the central visual pathway.

The Second Face of Blindness: Processing Speed Deficits in the Intact Visual Field after Pre- and Post-Chiasmatic Lesions

Purpose Damage along the visual pathway results in a visual field defect (scotoma), which retinotopically corresponds to the damaged neural tissue. Other parts of the visual field, processed by the uninjured tissue, are considered to be intact. However, perceptual deficits have been observed in the “intact” visual field, but these functional impairments are poorly understood. We now studied temporal processing deficits in the intact visual field of patients with either pre- or post-chiasmatic lesions to better understand the functional consequences of partial blindness. Methods Patients with pre- (n = 53) or post- chiasmatic lesions (n = 98) were tested with high resolution perimetry – a method used to map visual fields with supra-threshold light stimuli. Reaction time of detections in the intact visual field was then analyzed as an indicator of processing speed and correlated with features of the visual field defect. Results Patients from both groups exhibited processing speed deficits in their presumably “intact” field as indicated by comparison to a normative sample. Further, in both groups processing speed was found to be a function of two factors. Firstly, a spatially restricted (retinotopic) influence of the scotoma was seen in longer reaction times when stimuli were presented in intact field sectors close to the defect. Secondly, patients with larger scotomata had on average longer reaction times in their intact field indicating a more general (non-retinotopic) influence of the scotoma. Conclusions Processing speed deficits in the “intact” visual field of patients with visual system damage demonstrate that visual system lesions have more widespread consequences on perception than previously thought. Because dysfunctions of the seeing field are expected to contribute to subjective vision, including visual tests of the presumed “intact” field may help to better understand vision loss and to improve methods of vision restoration and rehabilitation.

“Sightblind”: Perceptual Deficits in the “Intact” Visual Field

Unilateral visual cortex lesions caused by stroke or trauma lead to blindness in contralateral visual field – a condition called homonymous hemianopia. Although the visual field area processed by the uninjured hemisphere is thought to be “intact,” it also exhibits marked perceptual deficits in contrast sensitivity, processing speed, and contour integration. Such patients are “sightblind” – their blindness reaches far beyond the primary scotoma. Studies showing perceptual deficits in patients’ intact fields are reviewed and implications of these findings are discussed. It is concluded that consequences of partial blindness are greater than previously thought, since perceptual deficits in the “intact” field likely contribute to subjective vision loss in patients with visual field defect. This has important implications for vision diagnosis and rehabilitation.

Alternating Current Stimulation for Vision Restoration after Optic Nerve Damage: A Randomized Clinical Trial

Background Vision loss after optic neuropathy is considered irreversible. Here, repetitive transorbital alternating current stimulation (rtACS) was applied in partially blind patients with the goal of activating their residual vision. Methods We conducted a multicenter, prospective, randomized, double-blind, sham-controlled trial in an ambulatory setting with daily application of rtACS (n = 45) or sham-stimulation (n = 37) for 50 min for a duration of 10 week days. A volunteer sample of patients with optic nerve damage (mean age 59.1 yrs) was recruited. The primary outcome measure for efficacy was super-threshold visual fields with 48 hrs after the last treatment day and at 2-months follow-up. Secondary outcome measures were near-threshold visual fields, reaction time, visual acuity, and resting-state EEGs to assess changes in brain physiology. Results The rtACS-treated group had a mean improvement in visual field of 24.0% which was significantly greater than after sham-stimulation (2.5%). This improvement persisted for at least 2 months in terms of both within- and between-group comparisons. Secondary analyses revealed improvements of near-threshold visual fields in the central 5° and increased thresholds in static perimetry after rtACS and improved reaction times, but visual acuity did not change compared to shams. Visual field improvement induced by rtACS was associated with EEG power-spectra and coherence alterations in visual cortical networks which are interpreted as signs of neuromodulation. Current flow simulation indicates current in the frontal cortex, eye, and optic nerve and in the subcortical but not in the cortical regions. Conclusion rtACS treatment is a safe and effective means to partially restore vision after optic nerve damage probably by modulating brain plasticity. This class 1 evidence suggests that visual fields can be improved in a clinically meaningful way. Trial Registration ClinicalTrials.gov NCT01280877

Visual rehabilitation: visual scanning, multisensory stimulation and vision restoration trainings.

Neuropsychological training methods of visual rehabilitation for homonymous vision loss caused by postchiasmatic damage fall into two fundamental paradigms: “compensation” and “restoration”. Existing methods can be classified into three groups: Visual Scanning Training (VST), Audio-Visual Scanning Training (AViST) and Vision Restoration Training (VRT). VST and AViST aim at compensating vision loss by training eye scanning movements, whereas VRT aims at improving lost vision by activating residual visual functions by training light detection and discrimination of visual stimuli. This review discusses the rationale underlying these paradigms and summarizes the available evidence with respect to treatment efficacy. The issues raised in our review should help guide clinical care and stimulate new ideas for future research uncovering the underlying neural correlates of the different treatment paradigms. We propose that both local “within-system” interactions (i.e., relying on plasticity within peri-lesional spared tissue) and changes in more global “between-system” networks (i.e., recruiting alternative visual pathways) contribute to both vision restoration and compensatory rehabilitation, which ultimately have implications for the rehabilitation of cognitive functions.