Optic Nerve Demyelination Research Articles

Tumor necrosis factor causes an increase in axonal transport of protein and demyelination in mouse optic nerve

Tumor necrosis factor causes an increase in axonal transport of protein and demyelination in mouse optic nerve

Neuromyelitis optica (Devic's syndrome) and pulmonary tuberculosis

Neuromyelitis optica and acute necrotic myelopathy occur in association with pulmonary tuberculosis. We studied 8 patients with either neuromyelitis optica (6), acute myelopathy (1), or acute optic neuropathy (1) in close temporal association with pulmonary tuberculosis, but with no evidence for CNS tuberculosis. Neurologic symptoms preceded the use of antituberculosis medication in 5 patients. Different patients showed similar clinical features, suggesting a consistent disease pattern. Autopsy examination (1 patient) revealed extensive spinal cord and optic nerve demyelination. We identified only 5 additional patients seen over the same period with idiopathic neuromyelitis optica, thus suggesting that the close temporal relationship to pulmonary tuberculosis is not coincidental. The syndrome is most likely due to an immune reaction to tuberculosis rather than the use of antituberculosis medication.

Visual Evoked Potentials in the Diagnosis of Multiple Sclerosis

ABSTRACT.Electrophysiological methods are useful in the detection of clinically silent lesions in patients with suspected multiple sclerosis (MS). While no specific visual evoked potential (VEP) abnormalities are pathognomonic for optic nerve demyelination, they are highly sensitive indicators of visual pathway dysfunction. The prevalence of abnormal VEPs increases with the likelihood of the diagnosis of MS even in those patients with no history of visual symptoms, and in many studies approaches 100% in patients with known optic neuritis. The yield of VEP abnormalities varies considerably with technique. Abnormalities may appear selectively for certain kinds of stimulus patterns, and most studies employing multiple stimuli report an additive effect on yield. Other methods of assessment, such as evoked potentials in other sensory modalities and neuroimaging, test other portions of the nervous system, and therefore give results which are complementary to VEP testing. However, pattern reversal VEPs are more ...

Paraneoplastic optic neuropathy with histopathological verification of absence of meningeal metastases

In a patient with known carcinoma of the kidney and bilateral optic neuropathy, postmortem histological investigation of the retina, and intra- and extraorbital portions of the optic nerves, was performed. Demyelination and axonal loss in optic nerves was the only abnormality seen. There was no evidence of meningeal carcinomatosis. As far as could be retraced, this is the first case in whom true paraneoplastic optic neuropathy has been histopathologically verified by investigation of the optic nerves in their entirety.

Quantitative analysis of labelled inner retinal proteins in experimental optic neuritis.

In order to determine if axonal transport changes in chronic experimental allergic encephalomyelitis (EAE) were due to blockade or increased discharge of fast transported proteins from the inner retina, we examined the presence of pulse labeled proteins in autoradiograms of the optic nerve head, retinal ganglion cell and nerve fiber layers of juvenile strain-13 guinea pigs with chronic EAE and normal controls. Quantitative analysis of silver grains, performed six and twenty-four hours following the intravitreal injection of tritiated leucine, showed a decrease in inner retinal radioactivity in those with EAE, whereas no difference was detected between the two groups after three days. Grain counts within the optic nerve heads of guinea pigs with EAE were reduced at all time intervals studied. These results are consistent with an increase in discharge of fast transported proteins from retinal ganglion cells into optic nerve axons and support our previous observations of increased radioactivity at the foci of optic nerve demyelination.

Reflections on the pathogenesis of optic (retrobulbar) neuritis in multiple sclerosis

The conditions which lead to a plaque of demyelination in the retrobulbar optic nerve are discussed. Growth of the plaque occurs along venules as small fingerlike sleeves which develop outwards from the contour of the plaque. This occurs slowly and at intervals; the very gradually expanding lesion remain for a long time clinically silent. It is here postulated that the change to clinical disease is induced if cells digesting myelin debris settle in a more distal part of the perivascular space of a vein, than during the subclinical phase. In sufficient numbers these cells will impede the movement of molecules from extra-cellular fluid surrounding nodes of Ranvier into cerebrospinal fluid. A restriction in this vital drainage pathway results in oedema causing distrubed signal transmission in neurons passing through the veins drainage territory. Depending on intensity this can induce the characteristics symptom of blurred vision. These concepts have been used to speculate on sequential changes in neurons and to relate them to various phases of the disease. This seems to be justified as the pattern evolved corresponds well with the clinical symptomatology.

Evidence for a T-cell related factor as the cause of demyelination in mice following Semliki Forest virus infection

Patchy demyelination throughout the central nervous system, including the optic nerve, is known to occur following infection with Semliki Forest virus (SFV) in Swiss/A 2G mice. An increase in the fast axonal transport of protein in optic nerves occurred before they showed signs of demyelination in Swiss/A 2G mice, heterozygous nude mice and nude mice reconstituted with T-cells. SFV infection, however, caused neither an increase in the fast axonal transport of protein, nor optic nerve demyelination in T-cell-deficient nude mice. Thus, the increase in both axonal transport and demyelination following SFV infection appear to be T-cell-mediated events, rather than direct effects of the virus.

Reactive glial cells in CNS demyelination contain both GC and GFAP

The glial cell response to anti-galactocerebroside (GC) induced demyelination of the cat optic nerve was studied using electron microscopy and immunocytochemistry. Oligodendrocytes, which are a primary target for anti-GC, were depleted in the early lesions but astrocytes survived and showed reactive changes. Astrocytic processes exhibited dual staining for both GC and glialfibrillary acidic protein, a feature not seen in astrocytes outside the lesion or in normal optic nerve. These reactive astrocytes did not stain for anti-myelin basic protein, nor did they contain myelin debris, making it unlikely that the GC immunoreactivity was due to phagocytosis of myelin. Rather, it is postulated that the presence of GC in these cells represents a process of dedifferentiation to a more primitive state in which both astrocytic and oligodendrocytic determinants are synthesized, and that these reactive glial cells may be precursors of a new population of remyelinating oligodendrocytes.

Remyelination follows antibody-induced central nervous system demyelination.

Remyelination after anti-galactocerebroside-induced demyelination in the guinea pig optic nerve was evident 17 days after the onset of demyelination. The tempo of remyelination was uniform for large- and small-diameter axons and progressed, with compaction and thickening of myelin sheaths. Demyelinated axons were found interspersed among remyelinated fibers and were consistently separated from oligodendrocytes by astrocytic processes. These findings indicate that central nervous system remyelination may occur after in vivo antibody-induced demyelination, but that new myelin formation may be limited by mechanical interference from astrocytic processes.

Optic nerve demyelination induced by human serum: patients with multiple sclerosis or optic neuritis and normal subjects.

We injected guinea pig optic nerves with serum from patients with MS or acute optic neuritis (ON), or normal subjects. Serum from 12 of 17 MS patients, 3 of 3 patients with ON, and 5 of 11 normal age- and sex-matched controls produced myelin vesiculation and demyelination 24 hours after injection. Nerves injected with demyelinating serum contained oligodendrocytes with pyknotic nuclei and edematous, rarefied cytoplasm. Nerves injected with serum that did not cause demyelination did not have these oligodendrocyte changes. Serum from normal subjects or patients with MS may induce in vivo demyelination in mammalian CNS.

Galactocerebroside antiserum causes demyelination of cat optic nerve

A model of immune-mediated optic nerve demyelination is described. Micro-injection of small volumes (< 5 μ l) of high titer polyclonal anti-Gal-C serum into the cat optic nerve resulted in a focal, highly selective demyelinative lesion followed by remyelination. Demyelination appears to be due to a dual effect of myelin and on oligadendrocytes. The numbers of these cels within the lesion were initially reduced but subsequently increased as remyelination occured.

Flash electroretinogram abnormalities in patients with clinically definite multiple sclerosis.

We studied the flash electroretinograms (ERGs) of 105 patients with multiple sclerosis who were divided into four groups. The first group had no history or clinical evidence of optic nerve dysfunction, the second and third groups had either left or right optic nerve disease respectively, and the fourth group had historical or clinical evidence of bilateral optic nerve disease. Statistical analysis of the data using analysis of variance (ANOVA) showed that the group of patients with no history or clinical evidence of optic nerve disease had no significant difference from the control group for their peak b-wave implicit times but the other three groups were significantly delayed on the affected side(s). Using the Mann-Whitney U-test we found all four patient groups had significantly greater absolute interocular latency differences from the control group. The electroretinal contribution to flash VEP delay was also investigated. In those patients with unilateral or bilateral optic nerve disease we found that in 14-31% of those patients with flash VEP delay there was also abnormal prolongation of the ERG b-wave. These results confirm a high incidence of retinal dysfunction in multiple sclerosis patients and may suggest that transynaptic degeneration of retinal structures occurs in optic nerve demyelination. The significant absolute interocular latency difference in particular may provide another electrophysiological parameter to establish a diagnosis of multiple sclerosis in suspect cases.

Spinal cord and optic nerve demyelination in experimental herpes simplex virus type 2 infection.

To produce a model of central nervous system (CNS) demyelination, three strains of herpes simplex virus type 2 (HSV-2) were injected intracerebrally into Swiss-Webster outbred mice. Animals developed pupillary abnormalities and leg weakness and, by light and electron microscopy, had focal lesions of primary demyelination in optic nerves and spinal cords. Oligodendrocytes and astrocytes in these lesions contained herpesvirus. Both mouse age and virus dose were important determinants of the rate and severity of the infectious process, as judged by mortality and clinical signs of disease. A low virus dose in older mice favored survival of neurologically abnormal mice beyond the acute stage of infection. When the MS, G, and 186 strains of HSV-2 were compared, no evidence of a major effect of virus strain on the clinical course or type of pathology was seen. This study demonstrates that HSV-2 can produce multifocal demyelination in the CNS in mice. The intracerebral route appears to be important in producing a model of more generalized demyelination unrelated to the site of injection than has been previously reported in other experimental herpesvirus infections. The possible relationship of this model to optic neuritis, neuromyelitis optica, and multiple sclerosis is discussed.

Experimental allergic encephalomyelitis: modification of optic nerve pathology by antecedent virus infection.

Strain 13 guinea pigs, sensitised with spinal cord and Freund's complete adjuvant at 18–21 days of age, developed an experimental allergic encephalomyelitis (EAE) characterised by a non-fatal first attack followed by recovery, then remissions and relapses in the majority of animals. Pretreatment with an i.p. injection of an avirulent strain (A 774) of Semliki forest virus at 1 day of age resulted in an EAE with an accelerated onset and enhanced mortality during the first attack. Unlike the acute phase pathology in unpretreated animals, optic nerve demyelination was observed at 14 days after neuroantigen sensitisation. In sections of optic nerve from virus-treated animals, endothelial cell vesicularisation was seen and the role of this change in disease exacerbation is discussed. Virus treatments of animals older than 1 day of age resulted in a failure to potentiate the disease. Virus inoculated simultaneously with spinal cord alone failed to act as an adjuvent. The mechanism of virus action in modifying the immunopathogenesis of EAE and its relevance to multiple sclerosis is discussed.

Myelin proteins, glycoproteins, and myelin-related enzymes in experimental demyelination of the rabbit optic nerve: sequence of events.

Wallerian degeneration of the rabbit optic nerve was investigated by the technique of retinal ablation which precludes edema, hemorrhage, or macrophage infiltration. After 8 days of degeneration, marked degradation of axons and some myelin abnormalities appeared in the optic nerve, optic chiasma, and optic tract. Myelin lesions were maximal 32 days after retinal destruction. The amount of material stained with a myelin dye decreased drastically between 32 and 90 days after the operation. Biochemical parameters gave the following sequence of events. The concentration of the major periodic acid--Schiff staining glycoproteins was decreased after 2 days, and 6 days later the presence of cholesterol esters was detected in the optic tissue. After 16 days of Wallerian degeneration, the specific activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase not associated with myelin decreased, indicating a possible de-differentiation of oligodendrocytes. Degradation of myelin basic protein became significant at 32 days and the amount of myelin isolated decreased later. The loss of myelin basic protein coincided with a reduction of myelin periodicity as measured in purified fractions by electron microscopy. These results show that secondary myelin destruction in the absence of edema, hemorrhage, or macrophages is a very slow process, and in this situation myelin undergoes a selective and sequential loss of its constituents.

West Indian amblyopia.

A series of 21 patients admitted to St Thomas' Hospital, Medical Ophthalmology Unit, with a diagnosis of West Indian or West African amblyopia is reported. Patients were investigated for haematological, biochemical, serological, and radiological abnormalities and particular attention was paid to dietary history. Patients admitted in recent years also underwent neurophysiological investigations. No definite correlation between visual loss and dietary or family history was found, and there was no evidence that the improvement in vision which occurred in just under half the patients on follow-up was related to treatment with hydroxocobalamin or multivitamins. Visual-evoked responses in 4 patients showed a prolonged latency suggesting optic nerve demyelination, while in only one case was the electro-oculogram definitely subnormal. These findings contrast with those in 'toxic' amblyopias and suggest that the syndrome of West Indian amblyopoa may be due to bilateral optic nerve demyelination of unknown aetiology rather than the effect of toxic substances or nutritional deficiency on the retina.

Simultaneous recording of the visual evoked response to flashes at different retinal locations

A method is described which will allow a number of small-angle stimulus visual evoked responses to be measured simultaneously, thus providing the practical possibility for mapping the responses from different retinal sites for patients suspected of patchy optic nerve demyelination. The technique consists of stimulating four different retinal locations concurrently with small emitting diodes (LEDS) and time-locking a computer data buffer to each stimulus. Tests showed that if all four LEDS were flashed randomly, the evoked response to any given LED was as though this LED was the only stimulus present.

The Ultrastructure of the Retina in Adult Metachromatic Leukodystrophy

A 46-year-old woman afflicted with biochemically proven metachromatic leukodystrophy had only mild optic atrophy shortly before her death. Repeated earlier ophthalmoscopic examinations had not revealed any retinal abnormalities. Light microscopy of the retina showed strong acid phosphatase activity in both enlarged ganglionic cells and pigment epithelial cells. Demyelination of both optic nerves was not noted. Ultrastructurally, membranous lysosomal residual bodies were confined to ganglionic cells. We found lipofuscin material in pigment epithelial cells, but also within metachromatic leukodystrophy-specific residual bodies of ganglionic cells. The presence of lipofuscin represents the "wear-and-tear" phenomenon, possibly enhanced by the metachromatic leukodystrophy.