There is experimental evidence of trans-synaptic retrograde degeneration of retinal ganglion cells following retrogeniculate visual pathway lesions in primate studies. Retinal nerve fibre loss in congenital homonymous hemianopia in humans is well recognized from clinical observation but the findings in acquired lesions have been controversial. Forty-eight persons were recruited and divided into three groups. Two groups were patients with retrogeniculate lesions. In the first group, the occipital damage had occurred during childhood or in adult life whilst the lesions in the second group were congenital. Inclusion criteria for the retrogeniculate lesions included: age >18 years at time of testing; homonymous hemianopia; no other ophthalmic or neurological disorder; and neuroimaging demonstration of occipital lobe damage. The third group had normal visual function. Measurement of the thickness of the peripapillary retinal nerve fibre layer by optical coherence tomography has been carried out in both eyes of each subject. The primary outcome is the peripapillary retinal nerve fibre layer thickness (RNT) in microns. The mean RNT in the eyes with temporal hemianopia (here called the 'crossing-fibre defect' eyes) is 79.8 mu (SD = 35.1 mu) in the acquired and 72.7 mu (SD = 33.2 mu) in the congenital. The mean RNT in eyes with nasal hemianopia (here called the 'non-crossing-fibre defect' eyes) is 83 mu (SD = 29.5 mu) in the acquired and 73.4 mu (SD = 26 mu) in the congenital. In the control group, the RNT measured 101.4 mu (SD = 36.6 mu) for the left eyes and 100.8 mu (SD = 35.4 mu) for the right eyes. In both crossing-fibre defect eyes and non-crossing-fibre defect eyes the mean RNT is significantly greater in the controls than in the hemianopia groups (P < 0.001). These data confirm that there is thinning of the retinal nerve fibre layer following both congenital and acquired lesions of the retrogeniculate visual pathway in humans. This is most likely to represent retinal ganglion cell loss in both congential and acquired groups. Furthermore the magnitude of the thinning is similar in both groups despite the fact that clinical observation has consistently found evidence of RNT thinning in cases of congenital but not in cases of acquired pathology. The data have also been analysed in 12 sectors around the optic disc: it has been shown that the RNT thinning follows the known trajectories of the crossing and non-crossing retinal ganglion cell axons approaching the disc.

Following damage to the human post-geniculate visual pathway retrograde trans-synaptic degeneration of the optic nerve fibres occurs. It has been known for some time from investigations carried out in primates that a decline in the number of retinal ganglion cells follows occipital lobectomy. However, this is not detectable in all species studied and whether this occurs in humans was controversial until recent studies that have shown that following lesions of the occipital lobe, the retinal nerve fibre layer thickness measured by optical coherence tomography is reduced and corresponding shrinkage of the optic tract can be demonstrated by magnetic resonance imaging. The time course of the degeneration in humans is, however, unknown. In the present study, we have used optical coherence tomography to demonstrate for the first time progressive thinning of the retinal nerve fibre layer following occipital lobe/optic radiation damage due to stroke. First, in a group of 38 patients the measurement was taken on a single occasion at a known time interval since the stroke, ranging from 6 days to 67 years. Here, a negative straight line relationship (linear regression r = 0.54, P < 0.001) was found between nerve fibre layer thickness and elapsed time since injury in log years, giving a rate of decline of 9.08 µm per log year after adjusting for age. This indicates a decelerating rate of loss that differs from the rate of decline found with chronological age in this same group, which shows a steady rate of thinning by 0.4 µm per year (P = 0.006) after adjusting for duration of the disease. In a second study serial measurements were taken following the acute event in a group of seven patients with homonymous hemianopia; here a negative straight line relationship was found between time and nerve fibre layer thickness in micrometres over a period of data collection beginning at a mean of 36.9 days post-stroke (range 5-112) and ending at a mean of 426.6 days post-stroke (range 170-917). Evidence from clinical observation (funduscopy) suggested that retrograde trans-synaptic degeneration occurred in humans only where the damage to the post-geniculate pathway occurred prenatally. The results reported herein add weight to the previous demonstration that this type of degeneration does indeed occur in the human visual system by showing that it can be monitored over time and hence may provide a model for trans-synaptic degeneration in the human central nervous system.

The findings indicate loss of retinal ganglion cells and may reflect degenerative change in the brain in these conditions. The retinal nerve fibre layer thickness may be used as a biological marker and may help to distinguish between optic neuritis associated with multiple sclerosis and optic neuritis in neuromyelitis optica.

Transsynaptic degeneration had already begun 18 months after lesion. Although there was no visible decrease in volume at this stage, the white matter integrity was compromised. Significant decrease in volume could be visualized at longer durations of hemianopia. This method of objectively assessing structural images provides an effective, noninvasive approach to monitor the timescale of optic tract degeneration.

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This study suggests left-/right-hemispherical asymmetry in the Geniculocalcarine tracts with field deficits being 3.5 times more likely following left-sided anterior temporal lobe resections compared with right-sided resections. This has significant implications on counselling patients for these procedures. MR tractography may provide an anatomical substrate for these clinical findings, perhaps revealing a more anterior course of the optic radiations within the temporal lobe in one hemisphere versus the other.

We conclude that TRD of the OT occurs in acquired and congenital hemianopia, is correlated with visual field loss, and is most severe in congenital cases. Understanding the pattern of TRD may help to predict effects of any visual rehabilitation training.

BackgroundNon-ataxic symptoms of spinocerebellar ataxias (SCAs) vary widely and often overlap with various types of SCAs. Duration and severity of the disease and genetic background may play a role in such phenotypic diversity. We conducted the study in order to study clinical characteristics of common SCAs in Thailand and the factors that may influence their phenotypes.Methods131 (49.43%) out of 265 Thai ataxia families with cerebellar degeneration had positive tests for SCA1, SCA2, Machado-Joseph disease (MJD) or SCA6. The study evaluated 83 available families including SCA1 (21 patients), SCA2 (15), MJD (39) and SCA6 (8). Comparisons of frequency of each non-ataxic sign among different SCA subtypes were analysed. Multivariate logistic regression analyses were undertaken to analyze parameters in association with disease severity and size of CAG repeat.ResultsMean ages at onset were not different among patients with different SCAs (40.31 ± 11.33 years, mean ± SD). Surprisingly, SCA6 patients often had age at onset and phenotypes indistinguishable from SCA1, SCA2 and MJD. Frequencies of ophthalmoparesis, nystagmus, hyperreflexia and areflexia were significantly different among the common SCAs, whilst frequency of slow saccade was not. In contrast to Caucasian patients, parkinsonism, dystonia, dementia, and facial fasciculation were uncommon in Thai patients. Multivariate logistic regression analysis demonstrated that ophthalmoparesis (p < 0.001) and sensory impairment (p = 0.025) were associated with the severity of the disease.ConclusionsWe described clinical characteristics of the 4 most common SCAs in Thailand accounting for almost 90% of familial spinocerebellar ataxias. There were some different observations compared to Caucasian patients including earlier age at onset of SCA6 and the paucity of extrapyramidal features, cognitive impairment and facial fasciculation. Severity of the disease, size of the pathological CAG repeat allele, genetic background and somatic heterogeneity of pathological alleles may influence clinical expressions of these common SCAs.