Retrograde Trans-synaptic Degeneration Research Articles

Optic Atrophy From Retrograde Transsynaptic Axonal Degeneration Following Pediatric Brain Injury.

The patterns of optic atrophy due to retrograde transsynaptic degeneration (RTSD) have not been well characterized in children. This study aimed to characterize optic atrophy in pediatric patients with focal intracerebral lesions. A retrospective review of children with optic atrophy and focal intracerebral lesions was conducted. Ophthalmic data were recorded, including visual acuity, color vision, formal automated visual fields and optical coherence tomography (OCT) of the peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell layer. Six patients (83.33% male) were included. The mean visual acuity (VA) of all eyes was 0.30 logMAR (20/40 Snellen), with no significant difference in the mean logMAR VA in the ipsilateral eye to the location of the lesion compared with the contralateral eye (0.30 vs 0.30, P = 1.000). Color vision (available in 5 patients) was normal in 2, mildly reduced in one and markedly reduced in 2. Bitemporal optic disc pallor was observed in 5 out of 6 patients. OCT data revealed that pRNFL thickness was most significantly diminished in the temporal (95% CI: -44.71 to -14.18 µm, P = 0.0021), inferotemporal (95% CI: -75.06 to -5.17 µm, P = 0.0294), and superotemporal (95% CI: -76.82 to -18.51 µm, P = 0.0055) sectors. Average pRNFL thickness was significantly reduced compared with normative data in both the ipsilateral (95% CI: -40.76 to -11.69 µm, P = 0.0003) and the contralateral eye (95% CI: -38.46 to -5.83 µm, P = 0.0063). When only nasal and temporal data were analyzed, mean pRNFL thickness was still diminished compared with normative data (95% CI: -33.01 to -9.77 µm, P = 0.0012). Children presenting with optic atrophy, particularly with bitemporal optic atrophy, should have neuroimaging to exclude any underlying serious intracranial pathology.

Training in Cortically Blinded Fields Appears to Confer Patient-Specific Benefit Against Retinal Thinning.

Damage to the adult primary visual cortex (V1) causes vision loss in the contralateral hemifield, initiating a process of transsynaptic retrograde degeneration (TRD). Here, we examined retinal correlates of TRD using a new metric to account for global changes in inner retinal thickness and asked if perceptual training in the intact or blind field impacts its progression. We performed a meta-analysis of optical coherence tomography data in 48 participants with unilateral V1 stroke and homonymous visual defects who completed clinical trial NCT03350919. After measuring the thickness of the macular ganglion cell and inner plexiform layer (GCL-IPL) and the peripapillary retinal nerve fiber layer (RNFL), we computed individual laterality indices (LI) at baseline and after ∼6months of daily motion discrimination training in the intact or blind field. Increasingly positive LI denoted greater layer thinning in retinal regions affected versus unaffected by the cortical damage. Pretraining, the affected GCL-IPL and RNFL were thinner than their unaffected counterparts, generating LI values positively correlated with time since stroke. Participants trained in their intact field exhibited increased LIGCL-IPL. Those trained in their blind field had no significant change in LIGCL-IPL. LIRNFL did not change in either group. Relative shrinkage of the affected versus unaffected macular GCL-IPL can be reliably measured at an individual level and increases with time post-V1 stroke. Relative thinning progressed during intact-field training but appeared to be halted by training within the blind field, suggesting a potentially neuroprotective effect of this simple behavioral intervention.

Spotlight on Trans-Synaptic Degeneration in the Visual Pathway in Multiple Sclerosis.

A putative mechanism of neurodegeneration in multiple sclerosis (MS) is trans-synaptic degeneration (TSD), whereby injury to a neuron leads to degeneration of synaptically connected neurons. The visual system is commonly involved in MS and provides an ideal model to study TSD given its well-defined structure. TSD may occur in an anterograde direction (optic neuropathy causing degeneration in the posterior visual pathway including the optic radiations and occipital gray matter) and/or retrograde direction (posterior visual pathway lesions causing retinal degeneration). In the current review, we discuss evidence supporting the presence of anterograde and retrograde TSD in the visual system in MS.

Quantifying Retrograde Trans-Synaptic Degeneration of the Visual Pathway in Multiple Sclerosis. (S9.008)

<h3>Objective:</h3> To develop a method for quantifying retrograde trans-synaptic degeneration (rTSD) in multiple sclerosis (MS) and investigate its association with demographic characteristics and visual function. <h3>Background:</h3> Neurodegeneration occurs early in MS, contributes to irreversible clinical disability, and is poorly mitigated by currently available treatments. rTSD is a phenomenon in which injury to one neuroaxonal unit propagates retrogradely, amplifying neuronal loss from MS lesions. There are no effective ways of quantifying rTSD in the visual pathway and its impact on visual function has not been elucidated. <h3>Design/Methods:</h3> In this cross-sectional single-center study, patients with MS (pwMS) and non-MS controls underwent clinical, standard automated perimetry and optical coherence tomography assessments. Using customized retinal layer segmentation in nasal and temporal hemimacular sectors, we developed an rTSD-index, which compares ganglion cell hemimacular projections corresponding to each cerebral hemisphere, with positive values reflecting right-hemisphere driven rTSD and vice versa, and absolute rTSD-index (ArTSD) values indicating severity. <h3>Results:</h3> A total of 79 pwMS and 23 non-MS controls were included (average age 45±13 and 37±14, 67% and 61% female, respectively). On average, pwMS had higher ArTSD values (mean difference 1.5, p=0.02). Evidence of rTSD was detected in 13/79 (16%) pwMS and 0/23 non-MS controls at an ArTSD threshold of 3.5. In pwMS, longer disease duration was associated with increased ArTSD severity (β=0.9 for each decade of increased disease duration, p=0.03). For each 1 point increase in ArTSD value, there was on average a 0.1 dB worsening in corresponding visual hemifield function after excluding subjects with optic neuritis history (p=0.02). <h3>Conclusions:</h3> rTSD-index is a novel method to quantify rTSD of the visual pathway in MS, which occurs in 1 out of 6 pwMS, is associated with longer disease duration and subclinical visual field defects. Future studies investigating its association with clinical disability, MRI findings, and methods to mitigate it are needed. <b>Disclosure:</b> Mr. Manukyan has nothing to disclose. Miss Zabala has nothing to disclose. Ms. Locke has nothing to disclose. Dr. Guerrero has nothing to disclose. Dr. Kaisey has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Kaisey has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Kaisey has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Genentech. Dr. Kaisey has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Eichhorn &amp; Eichhorn, LLP. The institution of Dr. Kaisey has received research support from NMSS. The institution of Dr. Kaisey has received research support from Race to Erase MS. Dr. Khodabakhsh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bausch and Lomb. Dr. Khodabakhsh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Johnson and Johnson. Dr. Khodabakhsh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bausch and Lomb. Dr. Khodabakhsh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bausch and Lomb. The institution of Dr. Sicotte has received research support from Biogen. The institution of Dr. Sicotte has received research support from PCORI. The institution of Dr. Sicotte has received research support from NIH. The institution of Dr. Sicotte has received research support from NMSS. Dr. Sicotte has a non-compensated relationship as a National Medical Advisory Committee Chair with National MS Society that is relevant to AAN interests or activities. The institution of Dr. Sati has received research support from National Multiple Sclerosis Society. The institution of Dr. Sati has received research support from National Institutes of Health. Dr. Sati has received publishing royalties from a publication relating to health care. The institution of Dr. Al-Louzi has received research support from the National Multiple Sclerosis Society and American Brain Foundation.

Evidence for and Against Subclinical Disease Activity and Progressive Disease in MOG Antibody Disease and Neuromyelitis Optica Spectrum Disorder

Objective To investigate the evidence for and against relapse-independent clinical progression and/or subclinical disease activity in patients with Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD) and Aquaporin-4 IgG Seropositive Neuromyelitis Optica Spectrum Disorder (AQP4-IgG+ NMOSD). Background MOGAD and AQP4-IgG+ NMOSD are generally relapsing disorders, without clinical progression or subclinical disease activity outside of relapses. With advances in the diagnosis and treatment of these conditions, prolonged periods of remission without relapses can be achieved, and the question of whether progressive disease courses can occur has re-emerged. Design/Methods We conducted a narrative literature review in Ovid MEDLINE and Embase, exploring the evidence for and against relapse-independent progression in MOGAD and AQP4-IgG+ NMOSD. We classified the results in four categories : 1)Clinical observations, 2)MRI findings, 3)Retinal imaging, and 4)Fluid-based biomarkers. Results As the optic nerve is the major site of involvement in MOGAD and AQP4-IgG+ NMOSD, much of the data comes from the visual pathway studies. Possible pathophysiologic mechanisms of the OCT abnormalities in the absence of symptomatic optic neuritis are: 1) primary neurodegenerative process in retina, 2) subclinical inflammation of the optic nerve, 3) chiasmal involvement leading to abnormal findings in the unaffected eye, and 4)trans-synaptic retrograde degeneration originating from inflammatory lesions in the posterior visual pathway. Except for chiasmal involvement, these mechanisms are not specific to the visual pathway, and are considered as potential explanations for subclinical disease activity outside of the retina. Outside of the visual pathway, there is a lack of sufficient evidence to support the existence of subclinical disease activity and/or relapse-independent clinical progression in MOGAD and AQP4-IgG+ NMOSD, although recent fluid-based biomarker data (serum NfL and GFAP) support that neuro-axonal and/or astrocytic damage may be ongoing between attacks in these diseases. Conclusions This review highlights the many unknowns that remain in our understanding of the pathophysiology and clinical course of MOGAD and AQP4-IgG+ NMOSD.

High sampling resolution optical coherence tomography reveals potential concurrent reductions in ganglion cell-inner plexiform and inner nuclear layer thickness but not in outer retinal thickness in glaucoma.

To analyse optical coherence tomography (OCT)-derived inner nuclear layer (INL) and outer retinal complex (ORC) measurements relative to ganglion cell-inner plexiform layer (GCIPL) measurements in glaucoma. Glaucoma participants (n= 271) were categorised by 10-2 visual field defect type. Differences in GCIPL, INL and ORC thickness were calculated between glaucoma and matched healthy eyes (n= 548). Hierarchical cluster algorithms were applied to generate topographic patterns of retinal thickness change, with agreement between layers assessed using Cohen's kappa (κ). Differences in GCIPL, INL and ORC thickness within and outside GCIPL regions showing the greatest reductions and Spearman's correlations between layer pairs were compared with 10-2 mean deviation (MD) and pattern standard deviation (PSD) to determine trends with glaucoma severity. Glaucoma participants with inferior and superior defects presented with concordant GCIPL and INL defects demonstrating mostly fair-to-moderate agreement (κ=0.145-0.540), which was not observed in eyes with no or ring defects (κ=-0.067-0.230). Correlations (r) with MD and PSD were moderate and weak in GCIPL and INL thickness differences, respectively (GCIPL vs. MD r= 0.479, GCIPL vs. PSD r= -0.583, INL vs. MD r= 0.259, INL vs. PSD r= -0.187, p= <0.0001-0.002), and weak in GCIPL-INL correlations (MD r= 0.175, p= 0.004 and PSD r= 0.154, p= 0.01). No consistent patterns in ORC thickness or correlations were observed. In glaucoma, concordant reductions in macular INL and GCIPL thickness can be observed, but reductions in ORC thickness appear unlikely. These findings suggest that trans-synaptic retrograde degeneration may occur in glaucoma and could indicate the usefulness of INL thickness in evaluating glaucomatous damage.

Non-vasogenic cystoid maculopathies.

Besides cystoid macular edema due to a blood-retinal barrier breakdown, another type of macular cystoid spaces referred to as non-vasogenic cystoid maculopathies (NVCM) may be detected on optical coherence tomography but not on fluorescein angiography. Various causes may disrupt retinal cell cohesion or impair retinal pigment epithelium (RPE) and Müller cell functions in the maintenance of retinal dehydration, resulting in cystoid spaces formation. Tractional causes include vitreomacular traction, epiretinal membranes and myopic foveoschisis. Surgical treatment does not always allow cystoid space resorption. In inherited retinal dystrophies, cystoid spaces may be part of the disease as in X-linked retinoschisis or enhanced S-cone syndrome, or occur occasionally as in bestrophinopathies, retinitis pigmentosa and allied diseases, congenital microphthalmia, choroideremia, gyrate atrophy and Bietti crystalline dystrophy. In macular telangiectasia type 2, cystoid spaces and cavitations do not depend on the fluid leakage from telangiectasia. Various causes affecting RPE function may result in NVCM such as chronic central serous chorioretinopathy and paraneoplastic syndromes. Non-exudative age macular degeneration may also be complicated by intraretinal cystoid spaces in the absence of fluorescein leakage. In these diseases, cystoid spaces occur in a context of retinal cell loss. Various causes of optic atrophy, including open-angle glaucoma, result in microcystoid spaces in the inner nuclear layer due to a retrograde transsynaptic degeneration. Lastly, drug toxicity may also induce cystoid maculopathy. Identifying NVCM on multimodal imaging, including fluorescein angiography if needed, allows guiding the diagnosis of the causative disease and choosing adequate treatment when available.

Full-field electroretinogram in evaluation of the outer retina in patients with multiple sclerosis

Background: Background: Optic nerve inflammation may contribute to the pathology of multiple sclerosis (MS) (retrograde trans-synaptic degeneration) However, within the past ten years, some investigations have indicated that primary retinopathy may be brought on by MS. This study used a full-field electroretinogram to test the function of the outer retinal layers in people with relapsing remitting multiple sclerosis (RRMS) (ff-ERG). Methods: This is a case- control study, conducted on 30 RRMS patients and 30 healthy controls. RRMS patients were subjected to neurological, ophthalmological, and radiological assessment. Both RRMS patients and controls were subjected to full field ERG. Results: The ff-ERG showed a significant delay of latencies of a and b-waves of both light and dark-adapted condition with reduction of their amplitudes compared to control. ERG responses were significantly affected in MS patients with or without optic neuritis compared to control. Most of ff-ERG parameters showed non statistically significant difference between optic neuritis and non-optic neuritis eyes. Conclusion: There is functional affection of the bipolar and the photoreceptors layers in the outer retina in optic neuritis and non-optic neuritis eyes of MS. Therefore, the outer retina could be a site for primary pathology in MS, unrelated to the optic nerve affection.

Lateral Geniculate Nucleus Volume Determined on MRI Correlates With Corresponding Ganglion Cell Layer Loss in Acquired Human Postgeniculate Lesions.

PurposeTo quantitatively assess lateral geniculate nucleus (LGN) volume loss in the presence of lesions in the postgeniculate pathway and its correlation with optical coherence tomography retinal parameters.MethodsThis was a case control study of patients recruited at the University Hospital Zurich, Switzerland. Nine patients who were suffering from lesions in the postgeniculate pathway acquired at least 3 months earlier participated. Retinal parameters were analyzed using spectral domain optical coherence tomography and a newly developed magnetic resonance imaging protocol with improved contrast to noise ratio was applied to measure LGN volume.ResultsThe affected LGN volume in the patients (mean volume 73.89 ± 39.08 mm3) was significantly smaller compared with the contralateral unaffected LGN (mean volume 131.43 ± 12.75 mm3), as well as compared with healthy controls (mean volume 107 ± 24.4 mm3). Additionally, the ganglion cell layer thickness corresponding with the affected versus unaffected side within the patient group differed significantly (mean thickness 40.5 ± 4.11 µm vs 45.7 ± 4.79 µm) compared with other retinal parameters. A significant linear correlation could also be shown between relative LGN volume loss and ganglion cell layer thickness decrease.ConclusionsCorresponding LGN volume reduction could be shown in patients with postgeniculate lesions using a newly developed magnetic resonance imaging protocol. LGN volume decrease correlated with ganglion cell layer thickness reduction as a sign of trans-synaptic retrograde neuronal degeneration.

Transsynaptic Ganglion Cell Degeneration in Adult Patients After Occipital Lobe Stroke.

Loss of retinal ganglion cells after occipital lobe damage is known to occur through transsynaptic retrograde degeneration in congenital lesions; however, studies of this phenomenon in acquired pathology, such as strokes affecting postgenicular visual pathway, are scant. We studied a cohort of adult patients with known onset of occipital lobe stroke to look for the presence, rate, and timing of macular ganglion cell loss on optical coherence tomography. Retrospective review of patients seen in tertiary neuro-ophthalmology practice with homonymous hemianopia secondary to occipital lobe stroke of known onset. Optical coherence tomography of the macular ganglion cell complex (GCC) was performed, and hemifields corresponding to the side of the visual field (VF) defect were compared with the control retinal hemifield. Fifteen patients with homonymous VF defects were included in the study, and 8 of these (53.3%) demonstrated GCC hemifield thickness of less than 90% on the side corresponding to VF loss including 2/9 (22%) patients who had a stroke less than 2.5 years ago and 6/6 (100%) patients who had a stroke longer than 2.5 years ago. The amount of hemifield atrophy correlated to the logarithm of time since stroke onset ( P =0.030) but not age ( P = 0.95) or mean deviation on VF ( P = 0.19). Three patients with longitudinal data showed GCC thinning rates of 1.99, 5.13, and 5.68 µm per year. Transsynaptic retrograde degeneration occurs after occipital lobe stroke as early as 5.5 months after injury and was observed in all patients 2.5 years after stroke.

Correlation Between Retrograde Trans-Synaptic Degeneration of Ganglion Cells and Optical Coherence Tomography Angiography Following Ischemic Stroke.

ObjectiveFollowing nerve injury, the projection of posterior visual pathway lesions into the macular ganglion cell layer (GCL) region indicates retrograde trans-synaptic degeneration (RTSD) as a mechanism of functional damage.Our purpose is to assess GCL damage and the impacts of ischemic brain lesions affecting the visual pathway on macular microvascularization in patients with stroke.MethodsIn a case-control study, we examined 15 ischemic stroke patients who showed visual field defects and 50 healthy controls using the high-resolution optical coherence tomography (OCT) techniques such as spectral domain-OCT (SD-OCT) to measure retinal nerve fiber layer (RNFL) and GCL thicknesses, and OCT angiography (OCTA) to assess damage to the macular microvasculature.ResultsIn the cases, the correlation was detected among the site of vascular damage, visual field defect, retinal GCL thinning, and normal RNFL thickness. Further observations were significant reductions in macular thickness, GCL thickness, outer retinal layer vascular density, and vascular area in deeper retinal layers (p < 0.05).ConclusionOur findings suggest that ocular microvasculature abnormalities could serve as diagnostic and/or prognostic markers in patients with stroke and support the described use of GCL thickness as an image marker of visual pathway RTSD after brain injury.

Astrocytic outer retinal layer thinning is not a feature in AQP4-IgG seropositive neuromyelitis optica spectrum disorders

BackgroundPatients with anti-aquaporin-4 antibody seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorders (NMOSDs) frequently suffer from optic neuritis (ON) leading to severe retinal neuroaxonal damage. Further, the relationship of this retinal damage...

Optic Tract Shrinkage Limits Visual Restoration After Occipital Stroke.

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. 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. 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. 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.

Cystic maculopathy of the inner nuclear layer in glaucoma patients

The study aimed to detect and describe glaucoma-related pseudocystic abnormalities at the internal nuclear layer (INL) of the macula using OCT, in relation with visual field defects and other clinical data. Primary open-angle glaucoma patients presenting for a follow-up visit were consecutively included over 5 months and underwent clinical examination, OCT imaging, and central 10-2 visual field testing. OCT measures included the thickness of the peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC), together with an analysis of B-Scans and en-face images. All data provided by OCT were analyzed and compared with the visual field testing. Fourteen patients out of 216 showed pseudocysts in the INL of the macula. These cysts were hyporeflective, fusiform, and of variable size (15 to 25μm) and were always associated with a thinning of both the RNFL and GCC. En-face OCT showed evidence of a distribution of cysts in the macular region, based on the appearance of numerous, dense hyporeflective pits whose localization matched precisely with the vision loss as assessed by central 10-2 visual field testing. No other correlations were found. Pseudocysts of the internal nuclear layer of the macular region are found in some cases of chronic glaucoma. Their presence is always associated with a scotoma in the visual field and appear to constitute a marker for glaucoma progression. Glaucoma-related central pseudocysts could result from Müller cell changes, excitotoxicity, and/or trans-synaptic retrograde degeneration. The presence of pseudocysts could be a marker of a particular subpopulation whose features remain to be determined.

Role for OCT in detecting hemi-macular ganglion cell layer thinning in patients with multiple sclerosis and related demyelinating diseases

ObjectiveInvestigations have found associations of homonymous thinning of the macular ganglion cell/ inner-plexiform layer (GCIPL) with demyelinating lesions in the post-chiasmal visual pathway among patients with multiple sclerosis (MS). Retinal thinning may also occur through retrograde trans-synaptic degeneration, a process by which lesions in post-geniculate visual pathway structures lead to thinning of the GCIPL across thalamic synapses. The purpose of our study was to determine the frequency of homonymous hemimacular thinning that occurs in association with post-chiasmal visual pathway demyelinating lesions in patients with MS and other demyelinating diseases. MethodsAdult patients with demyelinating diseases (MS, neuromyelitis optica spectrum disorder [NMOSD], myelin oligodendrocyte glycoprotein antibody disease (anti-MOG)) who were participants in an ongoing observational study of visual pathway structure and function were analyzed for the presence of hemimacular GCIPL thinning on OCT scans. Brain MRI scans were examined for the presence of post-geniculate visual pathway demyelinating lesions. ResultsAmong 135 participants in the visual pathway study, 5 patients (3.7%) had homonymous hemimacular GCIPL thinning. Eleven patients (8.1%) had a whole+half pattern of GCIPL thinning, characterized by hemimacular thinning in one eye and circumferential macular thinning in the contralateral eye. All but one patient with homonymous hemimacular thinning had demyelinating lesions in the post-geniculate visual pathway; however, these lesions were located in both cerebral hemispheres. ConclusionHomonymous hemimacular thinning in the GCIPL by OCT is associated with post-chiasmal visual pathway demyelinating lesions but it appears to be a relatively uncommon contributor to GCIPL loss. Patients with this pattern of GCIPL often fail to complain of hemifield visual loss. Future studies with prospective and detailed MR imaging may be able to more closely associate demyelinating lesions in anatomically appropriate regions of the post-chiasmal visual pathways with homonymous hemimacular thinning.

Direct and transsynaptic retrograde degeneration and optic nerve head microvascular changes in patients with hemianopia

To investigate optic nerve head (ONH) microvascular changes secondary to transsynaptic retrograde degeneration (TRD), comperatively with direct retrograde degeneration and healthy controls. Patients with hemianopia due to intracranial lesion included in the study. Intracranial lesion was categorized by location: postgeniculate (causing TRD), chiasmal (causing direct retrograde degeneration). For the postgeniculate lesions, the eye on the same side of the lesion was defined as the ipsilateral eye and the eye on the opposite side as the contralateral eye. Optic disc microvasculature was evaluated with the help of optic coherence tomography angiography. Sixteen eyes of 16 patients with chiasmal lesion, 28 eyes of 14 patients with postgeniculate lesion, and 30 eyes of 30 healthy subjects were included in the study. Ipsilateral eyes of the patients with postgeniculate lesion had decreased vessel density at the temporal sectors compatible with the affected nasal side of the visual field. Contralateral eyes showed no reduction of the vessel density at the affected nasal sectors. The eyes with chiasmal lesions had decreased vessel density at the peripapillary region and nasal half of the ONH compatible with temporal hemianopia. Vascular changes in the chiasmal lesion were more prominent than those of the postgeniculate lesion. Retinal nerve fiber layer and ganglion cell complex thickness were reduced. Vessel density of ONH was reduced in patients with homonymous hemianopia, providing evidence for TRD secondary to acquired postgeniculate lesion. Direct retrograde degeneration was more prominent in affected sectors when compared to TRD.

Retinal Changes After Posterior Cerebral Artery Infarctions Display Different Patterns of the Nasal und Temporal Sector in a Case Series

Background: Visual field defects are a common and disabling consequence of stroke and a negative prognostic factor of patient's quality of life. They result from lesions in different parts of the visual system, most commonly the visual cortex and optic radiation. An important pathophysiological mechanism is transsynaptic retrograde degeneration (TRD).Methods: In a case series 21 patients with posterior cerebral artery (PCA) territory infarctions were analyzed by spectral-domain optical coherence tomography (SD-OCT) and multifocal visual evoked potentials (mfVEPs) cross-sectionally and longitudinally for up to 6 months. In OCT, symptomatic affected nasal and temporal sectors and corresponding visual fields in mfVEPs were compared to the contralateral side.Results: SD-OCT revealed a significant reduction (−2.92 ±2.53 μm, mean ± SD) of the symptomatic nasal macular retinal nerve fiber layer (RNFL) thickness and of the symptomatic temporal peripapillary RNFL after 6 months compared to baseline whereas the symptomatic temporal macular quadrant already showed a significantly thinner RNFL at baseline. The mfVEP first peak latency at baseline was significantly different (nasal visual field +11.69 ±11.17 ms, mean ± SD; temporal visual field +16.63 ±7.97 ms, mean ± SD) on the symptomatic compared to the asymptomatic field. The nasal visual fields partly recovered in amplitude and first peak latency of mfVEPs over the following 6 months compared to baseline.Conclusion: The dynamics of OCT and mfVEP outcomes for degeneration and recovery after PCA infarction differ between the nasal and temporal retinal sector. We postulate that retinal sectors may differ in their temporal pattern of TRD over time after retrogeniculate cerebral infarction.

Progressive secondary exo-focal dopaminergic neurodegeneration occurs in not directly connected midbrain nuclei after pure motor-cortical stroke

Transsynaptic anterograde and retrograde degeneration of neurons and neural fibers are assumed to trigger local excitotoxicity and inflammatory processes. These processes in turn are thought to drive exo-focal neurodegeneration in remote areas connected to the infarcted tissue after ischemic stroke. In the case of middle cerebral artery occlusion (MCAO), in which striato-nigral connections are affected, the hypothesis of inflammation-induced remote neurodegeneration is based on the temporal dynamics of an early appearance of inflammatory markers in midbrain followed by dopaminergic neuronal loss. To test the hypothesis of a direct transsynaptic mediation of secondary exo-focal post-ischemic neurodegeneration, we used a photochemical induction of a stroke (PTS) in Sprague-Dawley rats restricted to motor cortex (MC), thereby sparing the striatal connections to dopaminergic midbrain nuclei. To dissect the temporal dynamics of post-ischemic neurodegeneration, we analyzed brain sections harvested at day 7 and 14 post stroke. Here, an unexpectedly pronounced and widespread loss of dopaminergic neurons occurred 14 days after stroke also affecting dopaminergic nuclei that are not directly coupled to MC. Since the pattern of neurodegeneration in case of a pure motor stroke is similar to a major stroke including the striatum, it is unlikely that direct synaptic coupling is a prerequisite for delayed secondary exo-focal post ischemic neurodegeneration. Furthermore, dopaminergic neurodegeneration was already detected by Fluoro-Jade C staining at day 7, coinciding with a solely slight inflammatory response. Thus, inflammation cannot be assumed to be the primary driver of exo-focal post-ischemic cell death. Moreover, nigral substance P (SP) expression indicated intact striato-nigral innervation after PTS, whereas opposing effects on SP expression after striatal infarcts argue against a critical role of SP in neurodegenerative or inflammatory processes during exo-focal neurodegeneration.

Homonymous hemiatrophy of ganglion cell layer from retrochiasmal lesions in the visual pathway.

To determine the temporal evolution, morphology, and frequency of macular ganglion cell atrophy in patients with retrochiasmal lesions of the visual pathway. In a consecutive retrospective case series, we identified 47 patients with homonymous hemianopia and accessible macular optical coherence tomography scans. We estimated the time of lesion onset and the location of the lesion within the afferent visual pathway. Using semiautomatic layer segmentation, we determined ganglion cell layer thickness in areas projecting to the side of the retrochiasmal lesion and compared it with ganglion cell layer thickness on the healthy side. We found that retrochiasmal lesions at any level may be associated with an atrophy of ganglion cells. This atrophy respects the vertical midline through the fovea and thus the anatomic separation of the nasal and temporal visual field. The vertical line separating the affected from the unaffected side has significantly less tilt as compared with the disc-fovea angle. Lesions of the optic tract are associated with earlier macular ganglion cell atrophy than retrogeniculate lesions. Macular ganglion cell atrophy may be present in cases with normal peripapillary nerve fiber layer analysis and vice versa. Macular ganglion cell layer thickness shows a topographic hemiatrophy in retrochiasmal lesions, which manifests earlier for tract lesions than for retrogeniculate lesions. This additional examination of ganglion cell homonymous hemiatrophy has a higher sensitivity in detecting retrograde transsynaptic degeneration than the analysis of the peripapillary nerve fiber layer alone.

Evaluation of Significance Maps and the Analysis of the Longitudinal Time Course of the Macular Ganglion Cell Complex Thicknesses in Acquired Occipital Homonymous Hemianopia Using Spectral-domain Optical Coherence Tomography

ABSTRACT The present study was performed to evaluate the ganglion cell complex (GCC) thickness as well as the significance map and analyse the time course of the change in GCC thickness in patients with homonymous hemianopia due to posterior cerebral artery (PCA) territory stroke using spectral-domain optical coherence tomography. This study included 40 control subjects and 11 patients with unilateral PCA territory stroke. The GCC parameters were quantified using a custom-built software programme. The GCC data, centred on the macula, was divided vertically into hemianopic and unaffected sides. GCC parameters were calculated using an average of those from both eyes. The relationship between the GCC parameters and the time after stroke was determined by regression analyses. The GCC parameters in the hemi-retinae corresponding to the affected hemifields significantly differed between the hemianopes and the control group. The area under the receiver operating characteristics curve of the GCC significance map areas was significantly high. A regression analysis revealed a significant relationship between the time after stroke and both the GCC significance map areas (r = 0.791, p = .004) and GCC thickness (r = −0.736, p = .010) on the hemianopic side. The GCC parameters on the hemianopic side were reduced in patients with acquired occipital homonymous hemianopia, and the reduction was slowly progressive probably due to transsynaptic retrograde degeneration of the retinal ganglion cells. A significance map analysis provides additional OCT parameters that could be used to investigate the effect of retrogeniculate lesions on the inner retina of patients.