Case report: hyperbaric oxygen and MRI findings in radiation-induced optic neuropathy.

Hyperbaric oxygen (HBO2) therapy has been utilized in conjunction with systemic corticosteroid administration for treating radiation-induced optic neuropathy (RON) with varying success. We present the case of a 78-year-old female with RON who received two courses of HBO2 (without corticosteroids) and also pre- and post-treatment magnetic resonance imaging (MRI) of her brain. Her visual acuity subjectively and functionally improved throughout her first course of 30 treatments, including regaining the ability to ambulate independently, but subsequently deteriorated following completion. A second course of 40 additional treatments was prescribed; the patient's visual symptoms subjectively improved once more, followed again with subsequent decline after treatment. Post-treatment MRI also showed resolution of previously visible optic nerve contrast enhancement. This patient represents the 27th reported case of RON treated with HBO2 and the first reported case of radiologic and transient symptomatic improvement without concomitant steroid use. Our case adds additional evidence to the limited anecdotal data supporting MRI correlation with RON symptoms and HBO2 in RON treatment as well.

The delayed cost of treatment.

A 78-year-old woman presented with acute decreased vision in both eyes. She had been treated for a pituitary mass with a total of 4,500 centigray of external beam radiation 8 months prior to presentation. She was diagnosed with radiation optic neuropathy. Treatment with hyperbaric oxygen and intravenous steroids were initiated but vision remained poor.

Neuroprotective effect on retinal ganglion cells by transpupillary laser irradiation of the optic nerve head.

This study demonstrates that subthreshold transpupillary thermotherapy (TTT) laser irradiation on optic nerve head protects retinal ganglion cells (RGCs) in an optic nerve crush (ONC) model. TTT was performed in right eyes with an 810-nm diode laser aimed at the center of the optic nerve head, using the following protocol: power 60mW, duration 60s, spot size 500mum. Fluoro-Gold was injected into bilateral superior colliculi 5 days before sacrifice and fluorescent gold labeled RGCs were counted under fluorescence microscopy. In the ONC group, a progressive loss of RGCs was observed; however, in comparison with the ONC group, RGCs density was significantly higher (P=0.001, independent samples t-test) at day 7 postoperative and only borderline significances were obtained at days 14 and 28 postoperative (P=0.044 and P=0.045, respectively, independent samples t-test) in ONC+TTT group, which implies the potential neuroprotective role of TTT. This protective effect seems to be heat shock proteins (HSPs) related, because intraperitoneal Quercetin (an inhibitor of HSPs, 4mg/kg/day for 7 days) could completely abolish this protective effect at days 7, 14 and 28 postoperative (P=0.012, P=0.002, and P=0.000, respectively, independent samples t-test). Minimal collateral damage of TTT on optic nerve head tissue, peripapillary RGCs and the myelin sheath of the optic nerve were observed under transmission electron microscopy. These findings suggested that subthreshold TTT might be a safe and practical approach to protect RGCs. The underlying mechanisms may involve TTT-induced HSPs in RGCs.

Optic neuropathy secondary to radiotherapy for nasal melanoma.

Optic neuropathy is a rare but important complication of radiotherapy used in the treatment of cancers of the head and neck, usually resulting in rapidly progressive blindness in one or both eyes. The case is presented of a 77-year-old woman with bilateral optic neuropathy resulting in blindness, secondary to radiotherapy for a melanoma of the nasal cavity. The onset of optic neuropathy occurred 9 months post-radiotherapy, at a cumulative dose of 6000 rad. The left eye was first involved, with the right eye becoming involved within 2 weeks. Despite treatment with oral anticoagulation and high dose intravenous methylprednisolone, there was progressive deterioration resulting in bilateral optic atrophy, with final visual acuities of perception of light in the right eye and no perception of light in the left eye. This case demonstrates that oral anticoagulation was ineffective in the treatment of progressive radiation-induced optic neuropathy.

[Potential mechanism of therapeutic effect of magnetic effect of magnetic field and photic stimulation on the nerve fibers in the visual tract]. / O vozmozhnom mekhanizme lechebnogo deistviia magnitnogo polia i svetovoi stimuliatsii na nervnye volokna zritel'nogo trakta.

Constant and alternating external magnetic fields induce a sedative effect due to Lorentz forces and also stimulate indirectly metabolic processes. With the properly chosen polarity of the inductor and its position relative to nerve fibers, and with asymmetric and inhomogeneous electrical conductivity in the vicinity of excited fibers, which can be enhanced by pattern light stimulation, magnetic fields produced by asymmetric impulses with one steep front (fore and back) can further enhance excitability and conductivity.

A new Cys2/His2 zinc finger gene, rKr1, expressed in oligodendrocytes and neurons.

The myelination of nerve fibers is essential for the function of the vertebrate nervous system as a prerequisite for fast saltatory conduction of action potentials. In the central nervous system (CNS), myelin is produced by oligodendrocytes. In order to identify gene regulatory proteins involved in the differentiation of this glial cell type or in the expression of myelin-specific genes, we have constructed a cDNA library from a highly enriched population of rat oligodendrocytes and screened this library for members of the Krüppel family of Cys2/His2 zinc finger proteins. One of the identified clones, named rKr1, encodes a novel protein of 650 amino acids which contains 12 carboxy-terminal zinc finger domains and an amino-terminal acidic domain. On Northern blots, a single rKr1 mRNA of 4.3 kb is detected. This message is present in all adult rat tissues tested, with the highest levels found in the CNS and testis. In situ hybridization on the P15 brain revealed that the transcript is expressed in differentiated oligodendrocytes and in subtypes of neurons. Particularly high message levels are found in motor neurons of the brainstem and the spinal cord. The modular structure of the rKr1 protein, in which a potential DNA binding region (the zinc fingers) is combined with a putative activation domain (the acidic region), suggests a function as sequence-specific transcriptional activator.

A new Cys2/His2 zinc finger gene, rKr2, is expressed in differentiated rat oligodendrocytes and encodes a protein with a functional repressor domain.

The function of the vertebrate nervous system is dependent on the proper myelination of its fiber tracts. Myelin of the CNS is produced by oligodendrocytes. To identify gene regulatory proteins expressed in this particular glial cell type, we isolated cDNAs coding for Cys2/His2 zinc finger proteins from a rat oligodendrocyte cDNA library. One clone, named rKr2 (rKr for rat Krüppel-type protein), encodes a protein with 19 carboxy-terminal zinc finger domains and an amino-terminal Krüppel-associated box domain. This amino-terminal domain of the rKr2 protein behaved as a strong transcriptional repressor module when fused to the DNA binding domain of yeast GAL4 and tested on an appropriate reporter construct. High levels of rKr2 mRNA in adult rat tissues were found only in the CNS and testis; in the CNS, the message was predominantly expressed in differentiated oligodendrocytes. The modular structure of the rKr2 protein (carboxy-terminal DNA binding domain, amino-terminal repressor module) and its expression pattern suggest that it acts as a sequence-specific transcriptional repressor in the myelin-producing glial cells of the CNS.

Visual loss following treatment of sphenoid sinus carcinoma.

A 71-year-old woman developed complete third nerve palsy and total blindness of the right eye one month after completing a course of radiotherapy for sphenoid sinus carcinoma over a 13-month period. Differential diagnosis included recurrence of the tumor, radiation-induced second neoplasm, empty sella with chiasmal prolapse and secondary chiasmal arachnoid adhesions, and radionecrosis. Magnetic resonance imaging demonstrated gadolinium contrast enhancement of the right intracranial optic nerve and chiasm, suggesting a radionecrosis process.

Effect of light on oxygen-induced retinopathy in the rat model. Light and OIR in the rat.

The purpose of this study was to establish whether exposure to intense lighting favors the development or aggravates experimental oxygen-induced retinopathy in the newborn rat. Five groups of Wistar rats were studied. The control group was maintained for the first 14 days of life under conditions of cyclical (12L:12D) lighting at 12 Lx in room air. Two other groups were subjected, for the same amount of time, to semi-darkness (2 Lx; 12L: 12D), one with room air and the other with supplemental 80% oxygen. The final two groups were exposed to the same room air and hyperoxic treatments under intense lighting conditions (600 Lx; 12L:12D). After the treatment period, four rats were randomly chosen from each group, sacrificed and their retinas examined under electron microscope. Marked structural changes were seen only in the photoreceptor outer segments of those rats exposed to intense light. In eighty-five of the remaining rats retinal vascular morphology was examined in retinal flat mounts after intracardiac injection of India ink. Retinopathy was observed in rats treated with hyperoxia but no significant differences could be attributed to the light conditions under which the retinopathic rats had been maintained. In the rest of the rats, axonal transport along the optical pathways was evaluated after intravitreal injection of (3H) taurine. In the two groups exposed to hyperoxia, axonal transport was altered, but less markedly in those exposed to intense lighting than in those exposed to semi-darkness. Intense illumination under conditions of normoxia favors axonal transport. Exposure to intense lighting does not seem to aggravate oxygen induced retinopathy in the rat though it does produce structural lesions of the photoreceptors.

Delayed radiation injury to the retrobulbar optic nerves and chiasm. Clinical syndrome and treatment with hyperbaric oxygen and corticosteroids.

Thirteen patients with delayed radiation injury to the optic nerves and chiasm were treated with hyperbaric oxygen (HBO) and corticosteroids. These patients experienced painless, abrupt loss of vision in one (6 patients) or both (7 patients) eyes between 4 and 35 months after receiving radiation doses of at least 4500 cGy to the region of the chiasm. Diagnostic evaluation including neuro-imaging and lumbar puncture showed no recurrent tumor and no other cause for visual loss. No patient's vision improved during treatment or follow-up lasting between 1 and 4 years. There were no serious complications of treatment.

Progressive visual failure in acromegaly following external pituitary irradiation.

Four out of twenty-three acromegalic patients selected for treatment with external megavoltage pituitary irradiation between 1961 and 1975 developed progressive visual failure. They had received megavoltage external irradiation through multiple portals from a cobalt-60 unit over a period of 3 weeks. Visual deterioration began 2 months to 6 years after irradiation. In two patients the optic nerves were explored. In both, post-mortem later confirmed radiation damage to the optic nerves and hypothalamus. In one case there was also necrosis of the right frontal lobe with necrosis and inflammation of the bone surrounding the pituitary fossa. In the two other patients, extensive clinical and neuroradiological investigation excluded the presence of a suprasellar mass as a cause for this visual failure and a clinical diagnosis of radiation necrosis was made.

Effects of single dose supervoltage whole brain radiation in Macaca mulatta.

Three groups of four Macaca mulatta were exposed respectively to a single dose of 1000, 1500, and 2000 rads of 20 MeV whole brain radiation with one animal from each group and a control scheduled for sacrifice at 6, 12, 18, and 24 months. With 1000 rads there were no abnormalities. The characteristic lesions in the animals exposed to 1500 and 2000 rads were small foci of delayed radiation necrosis that in the acute phase were relatively large due to marked local accumulation of edema fluid and at later stages were decreased in volume and showed early mineralization. Correspondingly the monkeys frequently showed papilledema, evidently from brain swelling, as the initial clinical finding, and upon histological examination at later stages, brain atrophy and ventricular dilatation. After exposure to 1500 rads the necrotic process was primarily in the white matter of the cerebral hemisphere and progressed from a small number of lesions in this location at 6 months to confluent necrosis at 12 months. At 18 and 24 months, although there was no evidence of further necrosis, there was evidence of increasing gliosis and at 24 months the occurrence of three independent glioblastomas. With exposure to 2000 rads there was a profuse wide scatter of focal necrotic lesions with a predilection for the basis pontis and a clinical deficit inconsistent with survival past 6 months. Accumulation of minute mineral deposits and atherosclerotic plaques were also noted in these monkeys and appeared to be related to both dose and survival time.