Ipsilateral Eye Research Articles

Surgical Management of Lesions of the Sphenoid Lateral Recess

Pneumatization of the sphenoid sinus occasionally includes an extensive lateral recess creating an area beneath the temporal lobe that is relatively inaccessible to surgical intervention. Pathology in this anatomic location presents special surgical and therapeutic challenges. Recently, several authors have described the endoscopic transpterygopalatine fossa approach to this anatomic region. This approach is associated with minimal morbidity while providing direct endoscopic surgical access for managing a variety of disease processes in this region. This study presents eight cases requiring this approach or a modification of this approach. Six patients presented with temporal lobe meningoencephaloceles with cerebrospinal fluid rhinorrhea. Each case was managed successfully through this surgical approach. One patient experienced transient postoperative palatal anesthesia due to injury to the greater palatine nerve and another complained of ipsilateral dry eye postoperatively. Two other patients had neoplasms (inverting papilloma and chondrosarcoma), which were successfully addressed through this technique. There were no postoperative complications in these patients. We have previously described the relationships of neural and vascular structures in this anatomic region. This article will review these relationships as they pertain to this surgical approach and will discuss the indications, techniques, and surgical outcomes in this series of patients. This approach is a valuable addition to the endoscopic armamentarium of the experienced endoscopic surgeon.

High dose rate brachytherapy with surface applicators: Treatment for nonmelanomatous skin cancer

15543 Background: To assess the use of HDR surface applicators as an alternative radiotherapy modality to external radiation (electrons or low-energy x-rays) for the treatment of skin lesions of the head and neck. Skin carcinomas require efficient and accurate delivery of HDR Brachytherapy, which can be precisely reproduced on an outpatient basis. Methods: Patients were treated to various sites, which included lesions of the face and scalp. Thermoplastic casts were fitted with Leipzig Surface Applicators and custom molded to the patient to treat squamous or basal cell carcinomas ≤ 2 cm in diameter. A custom surface mold applicator (Freiburg Flap) was used for lesions up to 4 cm. Planning target volume included the tumor plus a 5 mm margin. Biweekly photographs of the treatment volume were taken for documentation and monitoring of radiation reactions. Treatment was delivered by HDR Brachytherapy (Ir-192), 5 Gy per fraction, twice per week for four weeks to a 5 mm depth. TLD’s were placed at the center of the treated volume under the applicator and at critical structures (i.e. lateral canthus of the ipsilateral eye, auditory canal or gingivolabial sulcus) twice during the course of treatment. Results: Patients’ setup and reproducibility were accurate and treatment time was short which added great convenience for the patients. With the HDR surface applicators, dose distribution was uniform in the surface of the skin and at 5 mm depth in the whole area of the applicator. Differences between the areas of maximum and minimum dose at this depth did not reach values higher than 5% of the prescribed dose. At the edges of the applicators, the dose gradient was sharp, with the detected dose at 5 mm from the applicator being negligible. An exudative radiation reaction was noted in some patients, which reversed with appropriate therapy. Conclusion: High Dose Rate Brachytherapy offers a highly effective treatment of skin carcinomas. Surface applicators, used in conjunction with HDR brachytherapy equipment, make a uniform dose distribution and sharp dose gradient at the edge of the treatment field. Surface applicators are easy and safe to use, and they fit very accurately for each fraction. These applicators have the ability to become the standard treatment for skin carcinomas in the near future. No significant financial relationships to disclose.

Distribution of ganglion cells in the pigeon retina labeled via retrograde transneuronal transport of the fluorescent dye rhodamine β-isothiocyanate from the telencephalic visual Wulst

The distribution of retinal ganglion cells (RGCs) providing input to the thalamofugal visual system in the pigeon was studied with an anatomical transneuronal transport technique using the fluorescent dye rhodamine β-isothiocyanate (RITC). Unilateral injections of RITC made into the telencephalic visual Wulst resulted in the retrograde (1) first-order labeling (FOL) of dorsal thalamic (n. dorsolateralis anterior and n. superficialis parvocellularis: SPC) and brainstem somata as well as (2) second-order labeling of other cell populations within the brain and of retinal ganglion cells in both eyes obtained after transneuronal transfer of the tracer from neurons labeled directly via FOL. The mapping and counting of labeled RGCs in retinal flat-mounts showed that they were mainly distributed within the nasal portion of the retinal yellow field (YF) and that their total numbers were consistently higher (averaging 57%) in the eye contralateral to the tracer injection. Labeled RGCs in the retinal red field (RF) represented 13.4% and 12.0% of total labeled cells in the ipsilateral and contralateral eye, respectively. Moreover, the average densities of labeled cells/mm 2 in the RF and YF were respectively 8.4 and 42.8 (ipsilateral) and 17.9 and 54.0 (contralateral). The preferential distribution of labeled RGCs within the nasal YF supports the notion that the thalamofugal visual system in the lateral-eyed pigeon is mainly concerned with viewing in the lateral visual field. Conversely, the relatively low numbers of labeled RGCs observed within the specialized RF indicate that, unlike the case in frontal-eyed bird species and mammals, this system does not appear to be involved in binocular visual processing.

Neural Correlates of the Dependence of Compensatory Eye Movements During Translation on Target Distance and Eccentricity

To stabilize objects of interest on the fovea during translation, vestibular-driven compensatory eye movements [translational vestibulo-ocular reflex (TVOR)] must scale with both target distance and eccentricity. To identify the neural correlates of these properties, we recorded from different groups of eye movement-sensitive neurons in the prepositus hypoglossi and vestibular nuclei of macaque monkeys during lateral and fore-aft displacements. All neuron types exhibited some increase in modulation amplitude as a function of target distance during high-frequency (4 Hz) lateral motion in darkness, with slopes that were correlated with the cell's pursuit gain, but not eye position sensitivity. Vergence angle dependence was largest for burst-tonic (BT) and contralateral eye-head (EH) neurons and smallest for ipsilateral EH and position-vestibular-pause (PVP) cells. On the other hand, the EH and PVP neurons with ipsilateral eye movement preferences exhibited the largest vergence-independent responses, which would be inappropriate to drive the TVOR. In addition to target distance, the TVOR also scales with target eccentricity, as evidenced during fore-aft motion, where eye velocity amplitude exhibits a "V-shaped " dependence and phase shifts 180 degrees for right versus left eye positions. Both the modulation amplitude and phase of BT and contralateral EH cells scaled with eye position, similar to the evoked eye movements during fore-aft motion. In contrast, the response modulation of ipsilateral EH and PVP cells during fore-aft motion was characterized by neither the V-shaped scaling nor the phase reversal. These results show that distinct premotor cell types carry neural signals that are appropriately scaled by vergence angle and eye position to generate the geometrically appropriate compensatory eye movements in the translational vestibulo-ocular reflex.

Ischemic Ocular Motor Nerve Palsyを発症した末期腎不全患者の3例

Three patients on long-term hemodialysis therapy presented with sudden-onset isolated abducent nerve palsy. Two patients had ipsilateral eye pain. Computed tomographic scan or magnetic resonance imaging of the head did not reveal intracranial lesions responsible for the palsy. During the follow-up, the abducent nerve palsy of all three patients was resolved. Based on these findings, the three patients were diagnosed as having ischemic ocular motor nerve palsy. Although patients with end-stage renal disease often possess risk factors for ischemic ocular motor nerve palsy (hypertension, diabetes and atherosclerosis), the occurrence of ischemic ocular motor nerve palsy in the course of end-stage renal disease is rare.

Rotational vestibular epilepsy from the temporo-parieto-occipital junction

Humans likely have multiple cortical areas for processing vestibular information rather than a primary vestibular cortex.1 The parietal, temporal, and frontal lobes contain areas that receive vestibular input, with the temporo-perisylvian vestibular cortex having a dominant role.2 Cortical stimulation studies and naturally occurring lesions such as strokes have helped map the human vestibular cortex. Alternatively, partial seizures can serve as a natural form of cortical stimulation for mapping human cortical function. Ictal EEG recordings demonstrate that the posterior portion of the middle frontal gyrus receives rotational vestibular input and can serve as the focus for epileptic rotational vertigo.3 Although previous studies implicate the parieto-temporal area as a focus for vestibular epilepsy,4 direct clinical evidence is lacking. We report a boy with partial epilepsy characterized by rotational vertigo and ipsilateral head and eye deviation with jerking eye movements triggered visually following a moving object. An otherwise healthy, developmentally normal 8-year-old boy was evaluated for a 3-year history of episodes of dizziness and eye jerking. These episodes lasted <1 …

Recruitment of local excitatory circuits in the superior colliculus following deafferentation and the regeneration of retinocollicular inputs

The local synaptic connectivity in the superficial gray layer of the superior colliculus (SC) was assessed following retinal ganglion cell axonal regeneration through a peripheral nerve graft into the SC of Lister Hooded rats, using in vitro brain slice techniques. Repair was effected between the ipsilateral eye and SC, following bilateral lesion of optic nerves and ablation of ipsilateral occipital cortex. Deafferentation surgery alone resulted in a complete loss of synaptic potentials of extrinsic origin, once both retinal and cortical inputs were removed. Stimulation of graft insertion sites elicited synaptic responses comprising monosynaptic and network-mediated depolarising events. This activity, together with similar spontaneous bursts of depolarising events and action potential firing, was generated by the activation of non-N-methyl-D-aspartate glutamate receptors. This behaviour may reflect the development of a local recurrent synaptic connectivity following the repair surgery, as both evoked and spontaneous responses developed into large long-lasting bursts of excitatory activity when inhibition mediated by GABA receptors was blocked. These results suggest that the ultrastructural changes in the superficial layers of the SC resulting from deafferentation are reflected functionally at the synaptic level in the target structure even after repair. Such changes are likely to compromise the ability of the target structure to function normally during information processing. Therefore, although axons regenerating along peripheral nerve grafts can make functional synaptic connections, their efficacy in activating the target structure will probably be compromised by local changes in synaptic connectivity.

Loss of Reflex Tearing: An Expected Consequence of Juvenile Nasopharyngeal Angiofibroma

To report the loss of reflex tearing after surgical treatment of juvenile nasopharyngeal angiofibroma (JNA). A retrospective case series of 8 patients with surgical extirpation of JNA from 1995 to 2003 in a major teaching hospital setting was studied for symptomatic xerophthalmia. One patient was lost to follow-up. Four of the remaining 7 patients reported a dry ipsilateral eye after surgical treatment of JNA. The location of the pterygopalatine ganglion and its associated fibers in the pterygopalatine fossa is directly adjacent to the location of origin of JNA. Lacrimal innervation passes through the pterygopalatine ganglion. Given the extensive nature of advanced JNA and mandate for complete surgical excision, lacrimal dysfunction should be considered an expected consequence of surgery. The loss of reflex tearing has not been reported as a consequence of JNA or its surgical treatment. C.

Effectiveness of noncoplanar IMRT planning using a parallelized multiresolution beam angle optimization method for paranasal sinus carcinoma

To determine the effectiveness of noncoplanar beam configurations and the benefit of plans using fewer but optimally placed beams designed by a parallelized multiple-resolution beam angle optimization (PMBAO) approach. The PMBAO approach uses a combination of coplanar and noncoplanar beam configurations for intensity-modulated radiation therapy (IMRT) treatment planning of paranasal sinus cancers. A smaller number of beams (e.g. 3) are first used to explore the solution space to determine the best and worst beam directions. The results of this exploration are then used as a starting point for determining an optimum beam orientation configuration with more beams (e.g. 5). This process is parallelized using a message passing interface, which greatly reduces the overall computation time for routine clinical practice. To test this approach, treatment for 10 patients with paranasal sinus cancer was planned using a total of 5 beams from a pool of 46 possible beam angles. The PMBAO treatment plans were also compared with IMRT plans designed using 9 equally spaced coplanar beams, which is the standard approach in our clinic. Plans with these two different beam configurations were compared with respect to dose conformity, dose heterogeneity, dose-volume histograms, and doses to organs at risk (i.e., eyes, optic nerve, optic chiasm, and brain). The noncoplanar beam configuration was superior in most paranasal sinus carcinoma cases. The target dose homogeneity was better using a PMBAO 5-beam configuration. However, the dose conformity using PMBAO was not improved and was case dependent. Compared with the 9-beam configuration, the PMBAO configuration significantly reduced the mean dose to the eyes and optic nerves and the maximum dose to the contralateral optical path (e.g. the contralateral eye and optic nerve). The maximum dose to the ipsilateral eye and optic nerve was also lower using the PMBAO configuration than using the 9-beam configuration, although this difference was not significant. The mean doses to the optic chiasm and brain are marginally lower using the PMBAO configuration than using 9-beam configuration. The maximum doses to the optic chiasm and brain are the same with the PMBAO configuration and the 9-beam configuration. Parallelized multiple-resolution beam angle optimization with an optimized noncoplanar beam configuration is an effective and practical approach for IMRT treatment planning. Five-beam treatment plans optimized using the PMBAO are at least equivalent to, and overall better than, the plans using 9 equally spaced coplanar beams.

Optical imaging of the intrinsic signal as a measure of cortical plasticity in the mouse

The responses of cells in the visual cortex to stimulation of the two eyes changes dramatically following a period of monocular visual deprivation (MD) during a critical period in early life. This phenomenon, referred to as ocular dominance (OD) plasticity, is a widespread model for understanding cortical plasticity. In this study, we designed stimulus patterns and quantification methods to analyze OD in the mouse visual cortex using optical imaging of intrinsic signals. Using periodically drifting bars restricted to the binocular portion of the visual field, we obtained cortical maps for both contralateral (C) and ipsilateral (I) eyes and computed OD maps as (C - I)/(C + I). We defined the OD index (ODI) for individual animals as the mean of the OD map. The ODI obtained from an imaging session of less than 30 min gives reliable measures of OD for both normal and monocularly deprived mice under Nembutal anesthesia. Surprisingly, urethane anesthesia, which yields excellent topographic maps, did not produce consistent OD findings. Normal Nembutal-anesthetized mice have positive ODI (0.22 +/- 0.01), confirming a contralateral bias in the binocular zone. For mice monocularly deprived during the critical period, the ODI of the cortex contralateral to the deprived eye shifted negatively towards the nondeprived, ipsilateral eye (ODI after 2-day MD: 0.12 +/- 0.02, 4-day: 0.03 +/- 0.03, and 6- to 7-day MD: -0.01 +/- 0.04). The ODI shift induced by 4-day MD appeared to be near maximal, consistent with previous findings using single-unit recordings. We have thus established optical imaging of intrinsic signals as a fast and reliable screening method to study OD plasticity in the mouse.

Cerebellar Disease Alters the Axis of the High-Acceleration Vestibuloocular Reflex

L. W. Schultheis and D. A. Robinson showed that the axis of the rotational vestibuloocular reflex (RVOR) cannot be altered by visual-vestibular mismatch ("cross-axis adaptation") when the vestibulocerebellum is lesioned. This suggests that the cerebellum may calibrate the axis of eye velocity of the RVOR under natural conditions. Thus we asked whether patients with cerebellar disease have alterations in the RVOR axis and, if so, what might be the mechanism. We used three-axis scleral coils to record head and eye movements during yaw, pitch, and roll head impulses in 18 patients with cerebellar disease and in a comparison group of eight subjects without neurologic disease. We found distinct shifts of the eye-velocity axis in patients. The characteristic finding was a disconjugate upward eye velocity during yaw. Measured at 70 ms after the onset of head rotation, the median upward gaze velocity was 15% of yaw head velocity for patients and <1% for normal subjects (P < 0.001). Upward eye velocity was greater in the contralateral (abducting) eye during yaw and in the ipsilateral eye during roll. Patients had a higher gain (eye speed/head speed) for downward than for upward pitch (median ratio of downward to upward gain: 1.3). In patients, upward gaze velocities during both yaw and roll correlated with the difference in anterior (AC) and posterior canal excitations, scaled by the respective pitch gains. Our findings support the hypothesis that upward eye velocity during yaw results from AC excitation, which must normally be suppressed by the intact cerebellum.

Binocular visual responses in cells of the rat dLGN

In the mammalian visual system the output of the retina reaches the cerebral cortex by means of a synaptic link within the thalamus, the dorsal lateral geniculate nucleus (dLGN). In higher mammals this structure is visibly laminated, such that input from the two eyes remains segregated, binocular responses in essence being seen first in the cerebral cortex. In the rat this segregation is less obvious. With only around 3-10% of retinal ganglion cells projecting axons to the ipsilateral dLGN, the dLGN may be considered basically monocular; however, these ipsilaterally projecting axons contact cells in a region described as the 'hidden lamina', whose physiological properties have not been well described. In the anatomical literature, there is some debate as to the possibility of cross-over between the terminations of the two eyes. Here, a population of cells physiologically receiving input from the ipsilateral eye is described--surprisingly, the majority (63%) had powerful, excitatory input from both eyes, suggesting a simple form of binocular integration at a stage earlier than previously described for other, more 'visually developed' species, in which thalamic binocular integration is complex.

Displacement of Rectus Muscle Pulleys by Torsional Muscle Surgery for Treatment of Full Macular Translocation-induced Incyclotropia

To elucidate the coronal plane locations of extraocular muscle (EOM) pulleys following torsional muscle surgery. Case report. A 76-year-old man underwent advancement of the anterior part of the inferior oblique muscle to treat full macular translocation-induced incyclotropia. Postoperatively, magnetic resonance imaging was used to obtain contiguous, 2-mm-thick coronal orbital images. On each MRI image, the cross-sectional area and center of the EOM was computed, and all rectus EOM positions were translated to the coordinate origin at the area centroid of the globe at the level of pulleys. The superior rectus pulley was displaced temporally, and the lateral rectus pulley was displaced inferiorly more than 2 SD from normal subjects. Coronal plane locations of EOM pulleys of the ipsilateral eye showed extorsion compared with that of the contralesional eye. Torsional muscle surgery causes an extorsional shift of the superior and lateral rectus pulleys.

A rodent model for artificial gravity: VOR adaptation and Fos expression

Vestibulo-ocular reflex (VOR) adaptation and brainstem Fos expression as a result of short radius cross-coupling stimuli were investigated to find neural correlates of the inherent Coriolis force asymmetry from an artificial gravity (AG) environment. Head-fixed gerbils (Meriones unguiculatus, N=79) were exposed, in the dark, to 60--90 minutes of cross-coupled rotations, combinations of pitch (or roll) and yaw rotation, while binocular horizontal, vertical, and torsional eye position were determined using infrared video-oculography. Centripetal acceleration in combination with angular cross-coupling was also studied. Simultaneous sinusoidal rotations in two planes (yaw with roll or pitch) provided a net symmetrical stimulus for the right and left labyrinths. In contrast, a constant velocity yaw rotation during sinusoidal roll or pitch provided the asymmetric stimulus model for AG. We found orthogonally oriented half-cycle VOR gain changes. The results depended on the direction of horizontal rotation during asymmetrical cross-coupling, and other aspects of the stimulus, including the phase relationship between the two rotational inputs, the symmetry of the stimulus, and training. Fos expression also revealed laterality differences in the prepositus and inferior olivary C subnucleus. In contrast the inferior olivary beta and ventrolateral outgrowth were labeled bilaterally. Additional cross-coupling dependent labeling was found in the flocculus, hippocampus, and several cortical regions, including the perirhinal and temporal association cortices. Analyses showed significant differences across the brain regions for several factors (symmetry, rotation velocity and direction, the presence of centripetal acceleration or a visual surround, and training). Finally, animals compensating from a unilateral surgical labyrinthectomy who received multiple cross-coupling training sessions had improved half-cycle VOR gain in the ipsilateral eye with head rotation toward the intact side. We hypothesize that cross-coupling vestibular training can benefit aspects of motor recovery or performance.

Gaze Deviation from Contralateral Pseudoperiodic Lateralized Epileptiform Discharges (PLEDs)

Summary: Pseudoperiodic lateralized epileptiform discharges (PLEDs) usually produce “negative” neurologic findings. This contrasts with seizures which typically induce cortical activation with “positive” clinical manifestations. Gaze preference may arise from ipsilateral frontal eye fields (FEFs) damage because of the unopposed action of an intact contralateral FEF. Epileptic nystagmus (EN) and gaze deviation (GD) can also occur with focal temporo‐parieto‐occipital or hemispheric seizures in awake or obtunded patients.A patient with old right frontal and parieto‐temporal cerebral infarctions manifested leftward gaze preference and deviation (without nystagmus) while alert and talking. Digitized EEG demonstrated PLEDs at ∼1 Hz over the right fronto‐central region, without electrographic seizures.This report illustrates that PLEDs without seizures may excite frontal regions proximate to the FEFs to produce contraversive gaze preference in an awake patient, and discusses putative mechanisms. Gaze deviation, in this case, was the principal clinical feature of PLEDs.

Ephrin‐A2 and ‐A5 influence patterning of normal and novel retinal projections to the thalamus: Conserved mapping mechanisms in visual and auditory thalamic targets

Sensory axons are targeted to modality-specific nuclei in the thalamus. Retinal ganglion cell axons project retinotopically to their principal thalamic target, the dorsal lateral geniculate nucleus (LGd), in a pattern likely dictated by the expression of molecular gradients in the LGd. Deafferenting the auditory thalamus induces retinal axons to innervate the medial geniculate nucleus (MGN). These retino-MGN projections also show retinotopic organization. Here we show that ephrin-A2 and -A5, which are expressed in similar gradients in the MGN and LGd, can be used to pattern novel retinal projections in the MGN. As in the LGd, retinal axons from each eye terminate in discrete eye-specific zones in the MGN of rewired wild-type and ephrin-A2/A5 knockout mice. However, ipsilateral eye axons, which arise from retinal regions of high EphA5 receptor expression and represent central visual field, terminate in markedly different ways in the two mice. In rewired wild-type mice, ipsilateral axons specifically avoid areas of high ephrin expression in the MGN. In rewired ephrin knockout mice, ipsilateral projections shift in location and spread more broadly, leading to an expanded representation of the ipsilateral eye in the MGN. Similarly, ipsilateral projections to the LGd in ephrin knockout mice are shifted and are more widespread than in the LGd of wild-type mice. In the MGN, as in the LGd, terminations from the two eyes show little overlap even in the knockout mice, suggesting that local interocular segregation occurs regardless of other patterning determinants. Our data demonstrate that graded topographic labels, such as the ephrins, can serve to shape multiple related aspects of afferent patterning, including topographic mapping and the extent and spread of eye-specific projections. Furthermore, when mapping labels and other cues are expressed in multiple target zones, novel projections are patterned according to rules that operate in their canonical targets.

Connections of contralaterally projecting isthmotectal axons and GABA-immunoreactive neurons in Xenopus tectum: An ultrastructural study

To investigate the circuitry that mediates binocular interactions in the tectum of Xenopus frogs, we have begun to identify the tectal cells that receive ipsilateral eye input relayed via the nucleus isthmi. Isthmotectal axons were labeled with horseradish peroxidase, and thin sections were labeled by postembedding immunogold reaction with antibodies to gamma-aminobutyric acid (GABA). Ultrastructural examination reveals that many isthmotectal axons terminate on GABA-immunoreactive dendrites. Other isthmotectal axons contact postsynaptic structures that are unlabeled but have an appearance consistent with previously described GABA-poor zones of GABA-immunoreactive dendrites. We also examined the unlabeled inputs to the dendrites that were postsynaptic to filled isthmotectal axons. The most common nonisthmic inputs to those dendrites were GABA-immunoreactive processes with symmetric morphology. Surprisingly, we found only one input with the retinotectal characteristics of densely packed round, clear vesicles and minimal GABA immunoreactivity. These results indicate that isthmotectal axons synapse onto inhibitory interneurons, that retinotectal and isthmotectal axons do not synapse close to each other on the same dendrites, and that inhibitory connections are the closest neighbors to isthmotectal synapses.

Jerky seesaw nystagmus in isolated internuclear ophthalmoplegia from focal pontine lesion

Dissociated abducting nystagmus of the contralesional eye on attempted gaze to the contralesional side is typical of internuclear ophthalmoplegia (INO).1 Rarely, dissociated torsional-vertical nystagmus, usually downbeat in the ipsilateral eye and intorsional in the contralateral eye,2,3 or ipsilesional torsional nystagmus4,5 may occur in INO. We report a patient with isolated INO and jerky seesaw nystagmus from a focal pontine lesion and discuss possible mechanisms of various torsional-vertical nystagmus accompanying INO. A 47-old-woman was admitted with sudden vertigo and oscillopsia. She had diabetes mellitus and previous history of left corona radiata infarction. On admission, she could hardly open the eyes owing to severe oscillopsia. In neutral gaze, she showed extorsional downbeat nystagmus in the right eye synchronous with intorsional upbeat nystagmus in the left eye (see the video on the Neurology Web site at www.neurology.org). The nystagmus was changed into mainly upbeating on upward gaze. On leftward gaze, she also showed adduction paresis of the right eye with dissociated abducting nystagmus in the left eye (right INO). Convergence was mildly impaired, probably from oscillopsia. Head tilt or skew deviation was not evident. The remainder of the neurologic examination was unrevealing. MRI of the brain disclosed a tiny lesion in the right dorsomedial pontine tegmentum, which corresponds to the known anatomic location of the medial longitudinal fasciculus (MLF) (figure, A through C; see page …

Increased Noise Level of Purkinje Cell Activities Minimizes Impact of Their Modulation during Sensorimotor Control

While firing rate is well established as a relevant parameter for encoding information exchanged between neurons, the significance of other parameters is more conjectural. Here, we show that regularity of neuronal spike activities affects sensorimotor processing in tottering mutants, which suffer from a mutation in P/Q-type voltage-gated calcium channels. While the modulation amplitude of the simple spike firing rate of their floccular Purkinje cells during optokinetic stimulation is indistinguishable from that of wild-types, the regularity of their firing is markedly disrupted. The gain and phase values of tottering's compensatory eye movements are indistinguishable from those of flocculectomized wild-types or from totterings with the flocculus treated with P/Q-type calcium channel blockers. Moreover, normal eye movements can be evoked in tottering when the flocculus is electrically stimulated with regular spike trains mimicking the firing pattern of normal simple spikes. This study demonstrates the importance of regularity of firing in Purkinje cells for neuronal information processing.

Subconjunctivally administered celecoxib-PLGA microparticles sustain retinal drug levels and alleviate diabetes-induced oxidative stress in a rat model

We have previously reported that repeated oral doses of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, reduced diabetes-induced retinal vascular endothelial growth factor (VEGF) expression [ Ayalasomayajula, S.P., Kompella, U.B., 2003. Celecoxib, a selective cyclooxygenase-2 inhibitor, inhibits retinal vascular endothelial growth factor expression and vascular leakage in a streptozotocin-induced diabetic rat model. Eur J Pharmacol 458, 283–289] and that retinal celecoxib delivery can be improved by several-fold following subconjunctival administration [ Ayalasomayajula, S.P., Kompella, U.B., 2004. Retinal delivery of celecoxib is several-fold higher following subconjunctival administration compared to systemic administration. Pharm Res 21, 1797–1804]. The objective of the current study was to determine whether polymeric microparticles of celecoxib sustain retinal drug levels following subconjunctival administration and alleviate diabetes-induced oxidative stress in a streptozotocin-induced diabetic rat model. Biodegradable poly (lactide-co-glycolide) (PLGA; 85:15) microparticles of celecoxib were prepared using solvent evaporation method and characterized for their size, morphology, encapsulation efficiencies, and in vitro release. The celecoxib-PLGA microparticles or solution containing 75 μg of celecoxib was administered subconjunctivally to one eye (ipsilateral) of Sprague Dawley rats and drug levels in the retina, vitreous, lens, and cornea of ipsilateral and contralateral eyes were determined on 1, 7, and 14 days using high-performance liquid chromatography (HPLC). The effect of subconjunctivally administered celecoxib-PLGA microparticles on oxidative stress in day 14 diabetic rat retinas was determined by measuring the retinal glutathione (reduced (GSH) and oxidized (GSSG)), thiobarbituric acid reactive substances, and 4-hydroxynonenal levels using spectrofluorometric and colorimetric methods. Solvent evaporation method produced spherical celecoxib-PLGA microparticles with mean diameters of 3.9±0.6 μm and 68.5% loading efficiency. These microparticles sustained celecoxib release during the 49-day in vitro release study. Subconjunctivally administered celecoxib-PLGA microparticles sustained retinal and other ocular tissue drug levels during the 14-day study in rats. No detectable celecoxib levels were observed in the contralateral eye. The celecoxib-PLGA microparticles significantly inhibited the diabetes-induced increases in thiobarbituric acid reactive substance ( P=0.012) and 4-hydroxynonenal levels ( P=0.029). The particles also inhibited the GSH depletion and the increase in GSSH/GSH ratio associated with diabetes but the effects were not statistically significant ( P=0.12). Thus, following subconjunctival administration, celecoxib-PLGA microparticles sustained retinal celecoxib delivery and inhibited diabetes-induced retinal oxidative damage, indicating their potential usefulness in treating diabetes-induced retinal abnormalities.