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Irradiation of meningiomas of the intracranial anterior visual pathway.

Twenty patients with progressive visual loss caused by intracranial meningiomas involving the anterior visual pathway were treated with irradiation alone (n = 4) or with irradiation combined with tumor excision (n = 16). Improvement in visual performance occurred in 13 patients; 2 patients experienced temporary improvement; and 5 others maintained stable visual function for up to 9.5 years (mean follow-up, 4.0 years). Radiotherapy seemed to have no effect in 2 patients. One patient experienced temporary improvement, but eventually died from spread of tumor. Only one definite complication of radiotherapy occurred and was related to excessive radiation dose (greater than 7,000 cGy). Irradiation in the range of 5,000 to 5,500 cGy was effective either alone or in combination with surgical excision. Serial assessment of visual acuity and fields allowed us to demonstrate and quantify improvement in our patients following radiotherapy; in contrast, follow-up computed tomographic studies rarely demonstrated reduced tumor size.

Combined Modality Therapy

Aneurysmal compression of the anterior visual pathways.

Ten patients with aneurysmal compression of the anterior visual pathways had visual loss, unilateral in 4 and bilateral in 6. There was no typical clinical presentation. Visual loss was acute or gradual, acuity sometimes fluctuated, and visual field testing was highly variable. The aneurysms were supraclinoid (four patients), carotid-ophthalmic (two), anterior communicating-anterior cerebral (three), and intracavernous carotid (one). Nine patients had successful clipping of their aneurysm, and in one, ipsilateral common carotid ligation was performed. Postoperatively, visual acuity was improved in six cases, unchanged in three, and worse in one.

Adult

Monoclonal antibodies differentiate neurofilament and glial filament proteins in the goldfish visual pathway: probes for monitoring neurite outgrowth from retinal explants.

The expression of the neurofilament proteins of the goldfish visual pathway reflects the degeneration and regeneration of the optic nerve after nerve crush. To monitor these processes, monoclonal antibodies (mAb) were generated to the intermediate filament proteins of this pathway. The predominant goldfish visual pathway intermediate filament proteins have a molecular weight of 58K and can be separated into 4 isoelectric variants, 2 of which are neuronal (ON1 and ON2) and 2 of which are non-neuronal (ON3 and ON4). The specificities of the mAbs were characterized biochemically and histologically. Immunoblot analysis demonstrated that 2 of the antibodies reacted specifically with the neurofilament proteins (ON1/ON2) and another antibody reacted specifically with the glial filament proteins (ON3/ON4) and with a 48K optic nerve protein of non-neuronal origin. Chymotrypsin digestion of the ON proteins and immunoblotting of the resulting fragments showed that the anti-ON1/ON2 mAbs were directed toward the variable domains of the filament proteins. In contrast, the anti-ON3/ON4 mAb was directed toward the 40K chymotrypsin-resistant region of the glial filament proteins containing the conserved intermediate filament core. When sections of optic nerve tissue were incubated with anti-ON1/ON2 or anti-ON3/ON4 mAbs, the staining resulted in either axonal or glial patterns, respectively. In retina, after optic nerve crush, anti-ON1/ON2 labeled retinal ganglion cells and Müller fibers. In contrast, prior to optic nerve crush, only Müller fibers were labeled. One of the neuronal-directed mAbs was used to decorate growing neurites from retinal explants; anti-ON1/ON2 reactivity appeared in a time-dependent manner that paralleled the expression of ON1/ON2 in vivo. Thus, the antibodies can differentiate these 2 types of goldfish intermediate filament proteins and can be used to monitor optic nerve regeneration in the goldfish visual pathway both in vivo and in vitro.

Animals

Are flash-evoked visual potentials useful for intraoperative monitoring of visual pathway function?

Flash-evoked visual potentials (VEPs) recorded from the scalp were used in a series of 35 patients with tumors along the visual pathway: 3 orbital tumors, 25 perisellar tumors, 4 intraventricular tumors, and 3 occipital lesions. Preoperatively, various combinations of impaired visual fields and visual acuity were observed in over 90% of the patients. A postoperative decrease in visual function was observed in 3 cases. Of the 25 perisellar lesions, 13 were operated through a standard frontotemporal craniotomy and 12 were operated through a transnasal-transsphenoidal approach. VEPs were highly susceptible to volatile anesthetics, and there was a significant incidence of spontaneous latency increases and amplitude decreases in a large number of patients. There was an unacceptably high number of cases with significant VEP alteration occurring without concomitant visual function change. During trepanation or the transnasal approach, a reversible potential loss was observed in 11 patients, a profoundly altered wave form was seen in 8 cases, and a loss of single peaks was observed in 15 patients. During dissection of the tumor, a reversible potential loss or a potential with unidentifiable peaks was found in 25 cases; however, the VEPs recovered during closure or in the recovery room. There was no correlation between intraoperative VEP changes and the postoperative changes in visual function. In only 1 patient with an insignificant postoperative decrease in visual acuity from 0.4 to 0.3 was there a concomitant intraoperative potential loss. The major conclusion of our findings is that light-emitting diode flash-evoked VEPs demonstrate intraoperative changes that appear too early and too prominently to be caused solely by manipulation of the optic pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Paraphenylenediamine: a new method for tracing human visual pathways.

Morphologic investigations of the human visual pathways have been limited by the infeasibility of modern neuroanatomical approaches. Although contemporary methods for tracing axon pathways (such as tracer injections and electrophysiology) have elucidated the visual system in experimental animals, these techniques cannot be similarly applied in humans. Thus, the present view of the neuroanatomy of the human visual system is based largely on experimental animal studies, classical simple observations of gross human brains, and clinical inference. We demonstrate use of the stain, paraphenylenediamine (PPD), in conjunction with standard methods of tissue preparation for transmission electron microscopy. Osmium precipitates on degenerating neural processes, resulting in a dark profile when examined by electron microscopy. PPD chelates the osmium in osmium tetroxide-fixed tissue, and thus becomes a light-opaque marker of degenerating processes. This technique allows the identification and tracing of degenerating or degenerated axons. Postmortem studies of six patients, four with documented optic nerve lesions, are presented. The degenerated retinal ganglion nerve fibers are followed with PPD and confirmed with electron microscopy. Previously proposed, primary visual projections are confirmed and new retinofugal pathways are demonstrated in the human brain.

Adult

Evaluation of visual pathways in multiple sclerosis. I. After-images compared to visual evoked potentials.

The value of flight of colours (FOC), i.e. the succession of coloured afterimages following light stimulation, in diagnosing and following visual impairment was evaluated in 65 patients with multiple sclerosis (MS). Previous optimistic reports of the use of a pocket flashlight (PFL) method could not be confirmed, and are ascribed to inadequate methods. An electronic flashlight (EFL) method developed by us, proved a significantly better diagnostic tool (61% abnormal versus 18% abnormal). The EFL method was diagnostically less sensitive than pattern reversal visual evoked potential (PR-VEP) (80% abnormal). It did, however, add to PR-VEP by diagnosing 16 eyes with normal PR-VEP latency. The EFL method reflected the degree of degenerative changes in the central visual pathways and may be of value in following the disease activity in MS. The potential of the EFL method may be further improved by proposed modifications.

Afterimage

Pattern electroretinography in patients with delayed pattern visual evoked potentials due to distal anterior visual pathway dysfunction.

Between March 1983 and January 1988 delayed pattern visual evoked potentials (PVEP) were observed in 67 patients with distal visual pathway dysfunction. Many of these patients had been referred for neurophysiological examination because of possible optic nerve dysfunction. These patients also had pattern electroretinography (PERG) performed which in all cases showed an abnormality of the main positive P50 component. None of these patients had an abnormality confined to the negative N95 component, the type of abnormality usually found if the PERG is abnormal in optic nerve disease. It is suggested that PERG recording should now be a routine adjunct to the PVEP in the assessment of anterior visual pathway dysfunction.

Adolescent

Reorganization of visual pathways following posthatching removal of one retina in pigeons.

Organization of visual pathways was studied in 2-month-old pigeons that underwent unilateral retinal removal on either the day of hatching (ERA, i.e., early retinal ablated) or the 9th day after hatching (LRA, i.e., late retinal ablated). A general size reduction of visual areas contralateral to the removed retina was found in ERA pigeons, which additionally showed an altered differentiation of thalamic visual targets as well as a different cytoarchitectonic arrangement of the superficial layers of the optic tectum. No comparable modifications were found in LRA pigeons. The retinal projections of the remaining eye were studied following intraocular injections of 3H-proline. Both in ERA and LRA pigeons, the distribution of retinofugal afferents to primary visual regions contralateral to the injected eye was similar to that of control pigeons. Anomalous ipsilateral projections from the remaining retina to primary retinorecipient regions were found in ERA pigeons only. Effects of early ablation of one retina on second-order visual connections were also studied. Following injections of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) into the visual Wulst contralateral to the operated eye, a smaller number of ipsilateral projecting thalamo-Wulst neurons was found as compared with control pigeons. In contrast, the contralateral thalamo-Wulst projections were increased. No changes in thalamo-Wulst projections were found following tracer injections into the opposite Wulst, i.e., ipsilateral to the operated eye. The present study demonstrates a substantial anatomical reorganization of both primary and secondary visual pathways following unilateral retinal removal immediately after hatching, when maturation of the visual system is not yet completed.

Animals

Visual pathway abnormalities in albinism and infantile nystagmus: VECPs and stereoacuity measurements.

The visual pathway of albinos is characterized by abnormal optic nerve fiber decussation with increased contralateral projection. This results in hemispheric asymmetry of monocular visually evoked cortical potentials (VECPs) and may be related to lack of stereopsis. Flash VECP, Random Dot E (RDE), and Titmus stereotest data were collected from 40 nystagmus patients, 19 albino and 21 with normal pigmentation. Data were compared with results obtained from 19 race- and age-matched normal subjects. All albino patients demonstrated hemispheric VECP asymmetries exceeding +/- 2.0 standard deviations from the normal mean, showing either delayed ipsilateral P latency (88%), reduced ipsilateral P amplitude (59%), or both (47%). None of the normally pigmented infantile nystagmus patients exceeded this criteria on either VECP measure. While only one albinotic patient showed positive RDE and stereofly results, 86% of normally pigmented nystagmus patients passed the stereofly test, 60% demonstrated 400 sec (Titmus) stereopsis, and 66% showed positive RDE results. These findings reveal that normally pigmented infantile nystagmus patients have variable degrees of stereopsis and no excessive abnormalities of optic nerve fiber decussation as evidenced by flash VECP. Additionally, this study verifies visual pathway abnormalities and the lack of stereopsis in albino nystagmus patients.

Albinism

Different susceptibilities of the geniculate and extrageniculate visual pathways to human Creutzfeldt-Jakob disease (a combined neurophysiological-neuropathological study).

Flash evoked visual potentials (FEPs) of 7 patients with advanced Creutzfeldt-Jakob disease (CJD) were compared with those recorded in 7 patients with senile dementia of the Alzheimer type (SDAT), in 13 age- and sex-matched healthy volunteers and in 7 neuropsychiatrically normal subjects whose occipital evoked responses were increased in amplitude (amplitude controls). Post-mortem examination was performed in 4 of 7 CJD patients in order to map pathological changes along the visual pathways, including the retino-geniculo-striate and extrageniculate pathways. Normal FEPs were typified by 2 constant early components (P1 and N2) followed by several (3 or more) late components that were characterized by marked interindividual variability. Amplitude controls had enlarged (from 14 to 44.8 microV, mean 25.7) P1 component. Both SDAT and CJD patients had normal early FEP waves (P1 and N2) and important alterations of the late FEP components. Moreover, a late positive component was responsible for abnormally enlarged FEPs (52.6 and 58.2 microV) in 2 CJD patients. Finally, electroretinograms, recorded in 1 CJD patient, were normal. These findings suggested relative functional integrity of the retino-geniculo-striate pathway associated with important dysfunction of the cortical visual processing in both SDAT and CJD patients. Pathological studies disclosed preservation of optic nerves, chiasmas, lateral geniculate nuclei and Gennari's strip of the striate cortex but associated with important spongiform change, neuronal loss and gliosis in the superior colliculi (layer II), pulvinar, extrastriate cortex and layers II-III, V and VI of the striate cortex. We conclude that different visual pathways have different susceptibilities to CJD: important functional and anatomical alterations of the intracortical and extrageniculate pathways contrast with relative preservation of the retino-geniculo-striate pathway.

Adult

Electrophysiologic evaluation of the visual pathway in children. Case reports.

Clinical findings and results of electrophysiologic evaluation of the visual pathway were studied in seven children ranging in age from 10 months to 13 years. Using skin electrodes for electroretinographic and visual evoked potential testing, we obtained reliable results without sedation or pupil dilation. The half-field stimulation was indispensable for localizing lesions along the visual pathway and thus for specific diagnosis.

Adolescent

Spread of Creutzfeldt-Jakob disease virus along visual pathways after intraocular inoculation.

We studied the targeting of spongiform lesions within the visual pathways after intraocular injection with the Fujisaki strain of Creutzfeldt-Jakob disease (CJD) virus. The first lesions were observed 18 weeks postinoculation in the most superficial layer of the superior colliculus and in the lateral geniculate body contralateral to the side of the inoculation. Asymmetrical lesions in the superior colliculus were found also in mice sacrificed at 19, 22, and 27 weeks postinoculation. These results demonstrate that CJD virus spreads within the CNS via central axons of the visual pathways following intraocular inoculation.

Animals

Use of the Pulfrich pendulum for detecting abnormal delay in the visual pathway in multiple sclerosis.

(1) Pulfrich's pendulum has been developed as a method for detecting abnormal delay in the visual pathway of patients with suspected multiple sclerosis. (2) Forty-one normal subjects gave a mean interocular latency difference of 2-4 +/- 1-8 msec on Pulfrich's pendulum. This mean +2 SD (6 msec) was taken as the limit of normal interocular latency difference by this method. (3) The test was assessed on 58 patients. Eighteen of these had definite multiple sclerosis, 9 had probable multiple sclerosis, and 8 had possible multiple sclerosis, according to clinical criteria. The remaining 23 patients did not conform with clinical criteria for multiple sclerosis, and served as neurological controls. Thirteen of these 23 patients had abnormal signs in the visual system. All the 58 patients also had visual evoked responses (VERs) recorded. (4) Interocular latency difference was outside the normal range in 9/18 with definite multiple sclerosis, in 3/9 with probably multiple sclerosis and in 2/8 with possible multiple sclerosis. (5) Interocular latency difference was outside the normal range in 2/23 patients with other neurological disorders. (6) There was a strong correlation between abnormality on the Pulfrich pendulum and on the VER for the multiple sclerosis group. (7) Individual results are compared with those from the VER. There was no significant correlation of the size and direction of the interocular latency difference obtained from the Pulfrich pendulum with that obtained from the VER, for any group. Possible reasons for this are discussed. (8) It is concluded that Pulfrich's pendulum is an easily performed and potentially useful subjective test for detecting abnormal dealy in the visual pathway in multiple sclerosis.

Adolescent

Sensitivity and integration in a visual pathway for circadian entrainment in the hamster (Mesocricetus auratus).

1. Light-induced phase shifts of the circadian rhythm of wheel-running activity were used to measure the photic sensitivity of a circadian pacemaker and the visual pathway that conveys light information to it in the golden hamster (Mesocricetus auratus). The sensitivity to stimulus irradiance and duration was assessed by measuring the magnitude of phase-shift responses to photic stimuli of different irradiance and duration. The visual sensitivity was also measured at three different phases of the circadian rhythm. 2. The stimulus-response curves measured at different circadian phases suggest that the maximum phase-shift is the only aspect of visual responsivity to change as a function of the circadian day. The half-saturation constants (sigma) for the stimulus-response curves are not significantly different over the three circadian phases tested. The photic sensitivity to irradiance (1/sigma) appears to remain constant over the circadian day. 3. The hamster circadian pacemaker and the photoreceptive system that subserves it are more sensitive to the irradiance of longer-duration stimuli than to irradiance of briefer stimuli. The system is maximally sensitive to the irradiance of stimuli of 300 s and longer in duration. A quantitative model is presented to explain the changes that occur in the stimulus-response curves as a function of photic stimulus duration. 4. The threshold for photic stimulation of the hamster circadian pacemaker is also quite high. The threshold irradiance (the minimum irradiance necessary to induce statistically significant responses) is approximately 10(11) photons cm-2 s-1 for optimal stimulus durations. This threshold is equivalent to a luminance at the cornea of 0.1 cd m-2. 5. We also measured the sensitivity of this visual pathway to the total number of photons in a stimulus. This system is maximally sensitive to photons in stimuli between 30 and 3600 s in duration. The maximum quantum efficiency of photic integration occurs in 300 s stimuli. 6. These results suggest that the visual pathways that convey light information to the mammalian circadian pacemaker possess several unique characteristics. These pathways are relatively insensitive to light irradiance and also integrate light inputs over relatively long durations. This visual system, therefore, possesses an optimal sensitivity of 'tuning' to total photons delivered in stimuli of several minutes in duration. Together these characteristics may make this visual system unresponsive to environmental 'noise' that would interfere with the entrainment of circadian rhythms to light-dark cycles.

Animals

Sarcoidosis of the anterior visual pathway: successes and failures.

Four patients with progressive visual deterioration were found to have sarcoidosis involving the anterior visual pathway. They all developed chiasmal dysfunction and bilateral optic neuropathy, which responded to megadose corticosteroid therapy. When an attempt was made to withdraw the corticosteroids, the patients experienced a recrudescence of visual dysfunction and were subsequently unable to tolerate the corticosteroid dose levels necessary to maximise their visual potential. Each patient was treated with high-voltage radiation therapy, totalling up to 4500 rads. The beneficial response obtained was temporary, and immunosuppressive therapy with azathioprine or chlorambucil was instituted, preventing further deterioration.

Adrenal Cortex Hormones

A second ascending visual pathway from the optic tectum to the telencephalon in the pigeon (Columba livia).

Previous studies in the pigeon (Karten and Revzin: Brain Res. 2:368-377, '66; Karten and Hodos: J. Comp. Neurol. 140:35-52, '70) have described an ascending tectofugal visual pathway from the optic tectum to the ectostriatum by way of the nucleus rotundus of the thalamus. This present study used anterograde autoradiographic and retrograde horseradish peroxidase pathway-tracing techniques to investigate another ascending tectofugal pathway in the pigeon. Injections of 3H-proline/leucine confirmed a previous report that the optic tectum projects to the nucleus dorsolateralis posterior of the thalamus (DLP). This projection is predominantly ipsilateral and is confined to a large-celled caudal region of the nucleus (DLPc); the rostral region of the nucleus (DLPr) is not tectorecipient. Injections of horseradish peroxidase in DLPc labeled cells predominantly ipsilaterally in layers 8-15 of the optic tectum. Injections of 3H-proline/leucine placed in the DLPc labeled a discrete region of the ipsilateral telencephalon. Similar injections of DLPr labeled a contiguous, but more rostral, region of the neostriatum intermedium. Nissl- and silver-stained material indicated that the region in which DLP terminates is cytoarchitecturally distinct from ventromedial ectostriatal core and belt. Injections of horseradish peroxidase at various locations in the neostriatal DLP terminal field demonstrated a rostrocaudal ordering of the DLP projection upon the neostriatum intermedium. Single-unit recording demonstrated that cells in DLPc respond to whole-field illumination at the same latency as cells in the nucleus rotundus, indicating that the tecto-DLPc-neostriatal pathway transmits visual information to the telencephalon. We suggest that comparable pathways may exist in both reptiles and mammals.

Animals

[Value of visual evoked potentials (VEP) in compression of the anterior visual pathway, especially in the area of the chiasm].

We investigated 86 patients by pattern half-field stimulation presenting clinically with temporal field-defects or with a mass causing compression of the visual pathways found by C.T.-scanning. Pattern half-field stimulation proved to be a very sensitive method for detecting a compression of the anterior visual pathways. In 65 cases the results of perimetry and VEP were congruent, 6 times the evoked potential was pathologic the perimetry showing no abnormalities, only 1 false negative VEP was observed. Thus we stress the importance of an investigation by VEP including half-field stimulation in all patients with suspected compression of the anterior visual pathways.

Evoked Potentials, Visual