Immunization Against Oxidized Elastin Exacerbates Structural and Functional Damage in Mouse Model of Smoke-Induced Ocular Injury.

Purpose: Age-related macular degeneration (AMD) is the leading cause of blindness in Western populations. While an overactive complement system has been linked to pathogenesis, mechanisms contributing to its activation are largely unknown. In aged and AMD eyes, loss of the elastin layer (EL) of Bruch's membrane (BrM) has been reported. Elastin antibodies are elevated in patients with AMD, the pathogenic significance of which is unclear. Here we assess the role of elastin antibodies using a mouse model of smoke-induced ocular pathology (SIOP), which similarly demonstrates EL loss. Methods: C57BL/6J mice were immunized with elastin or elastin peptide oxidatively modified by cigarette smoke (ox-elastin). Mice were then exposed to cigarette smoke or air for 6 months. Visual function was assessed by optokinetic response, retinal morphology by spectral-domain optical coherence tomography and electron microscopy, and complement activation and antibody deposition by Western blot. Results: Ox-elastin IgG and IgM antibodies were elevated in ox-elastin immunized mice following 6 months of smoke, whereas elastin immunization had a smaller effect. Ox-elastin immunization exacerbated smoke-induced vision loss, with thicker BrM and more damaged retinal pigment epithelium (RPE) mitochondria compared with mice immunized with elastin or nonimmunized controls. These changes were correlated with increased levels of IgM, IgG2, IgG3, and complement activation products in RPE/choroid. Conclusions: These data demonstrate that SIOP mice generate elastin-specific antibodies and that immunization with ox-elastin exacerbates ocular pathology. Elastin antibodies represented complement fixing isotypes that, together with the increased presence of complement activation seen in immunized mice, suggest that elastin antibodies exert pathogenic effects through mediating complement activation.

Transplanted hESC-Derived Retina Organoid Sheets Differentiate, Integrate, and Improve Visual Function in Retinal Degenerate Rats.

Purpose: To investigate whether sheets of retina organoids derived from human embryonic stem cells (hESCs) can differentiate, integrate, and improve visual function in an immunodeficient rat model of severe retinal degeneration (RD). Methods: 3D hESC-derived retina organoids were analyzed by quantitative PCR and immunofluorescence. Sheets dissected from retina organoids (30-65 days of differentiation) were transplanted into the subretinal space of immunodeficient rho S334ter-3 rats. Visual function was tested by optokinetic testing and electrophysiologic recording in the superior colliculus. Transplants were analyzed at 54 to 300 days postsurgery by immunohistochemistry for donor and retinal markers. Results: Retina organoids contained multiple retinal cell types, including progenitor populations capable of developing new cones and rods. After transplantation into an immunodeficient rat model of severe RD, the transplanted sheets differentiated, integrated, and produced functional photoreceptors and other retinal cells, according to the longer human developmental timetable. Maturation of the transplanted retinal cells created visual improvements that were measured by optokinetic testing and electrophysiologic recording in the superior colliculus. Immunohistochemistry analysis indicated that the donor cells were synaptically active. Extensive transplant projections could be seen within the host RD retina. Optical coherence tomography imaging monitored long-term transplant growth and survival up to 10 months postsurgery. Conclusions: These data demonstrate that the transplantation of sheets dissected from hESC-derived retina organoids is a potential therapeutic method for restoring vision in advanced stages of RD.

Retinoic Acid Maintains Function of Neural Crest-Derived Ocular and Craniofacial Structures in Adult Zebrafish.

Purpose: Retinoic acid (RA) is required for embryonic formation of the anterior segment of the eye and craniofacial structures. The present study further investigated the role of RA in maintaining the function of these neural crest-derived structures in adult zebrafish. Methods: Morphology and histology were analyzed by using live imaging, methylacrylate sections, and TUNEL assay. Functional analysis of vision and aqueous humor outflow were assayed with real-time imaging. Results: Both decreased and increased RA signaling altered craniofacial and ocular structures in adult zebrafish. Exogenous treatment with all-trans RA for 5 days resulted in a prognathic jaw, while inhibition of endogenous RA synthesis through treatment with 4-diethylaminobenzaldehyde (DEAB) decreased head height. In adult eyes, RA activity was localized to the retinal pigment epithelium, photoreceptors, outer plexiform layer, inner plexiform layer, iris stroma, and ventral canalicular network. Exogenous RA increased apoptosis in the iris stroma and canalicular network in the ventral iridocorneal angle, resulting in the loss of these structures and decreased aqueous outflow. DEAB, which decreased RA activity throughout the eye, induced widespread apoptosis, resulting in corneal edema, cataracts, retinal atrophy, and loss of iridocorneal angle structures. DEAB-treated fish were blind with no optokinetic response and no aqueous outflow from the anterior chamber. Conclusions: Tight control of RA levels is required for normal structure and function of the adult anterior segment. These studies demonstrated that RA plays an important role in maintaining ocular and craniofacial structures in adult zebrafish.

Early alpha-lipoic acid therapy protects from degeneration of the inner retinal layers and vision loss in an experimental autoimmune encephalomyelitis-optic neuritis model.

BACKGROUND: In multiple sclerosis (MS), neurodegeneration is the main reason for chronic disability. Alpha-lipoic acid (LA) is a naturally occurring antioxidant which has recently been demonstrated to reduce the rate of brain atrophy in progressive MS. However, it remains uncertain if it is also beneficial in the early, more inflammatory-driven phases. As clinical studies are costly and time consuming, optic neuritis (ON) is often used for investigating neuroprotective or regenerative therapeutics. We aimed to investigate the prospect for success of a clinical ON trial using an experimental autoimmune encephalomyelitis-optic neuritis (EAE-ON) model with visual system readouts adaptable to a clinical ON trial. METHODS: Using an in vitro cell culture model for endogenous oxidative stress, we compared the neuroprotective capacity of racemic LA with the R/S-enantiomers and its reduced form. In vivo, we analyzed retinal neurodegeneration using optical coherence tomography (OCT) and the visual function by optokinetic response (OKR) in MOG35-55-induced EAE-ON in C57BL/6J mice. Ganglion cell counts, inflammation, and demyelination were assessed by immunohistological staining of retinae and optic nerves. RESULTS: All forms of LA provided equal neuroprotective capacities in vitro. In EAE-ON, prophylactic LA therapy attenuated the clinical EAE score and prevented the thinning of the inner retinal layer while therapeutic treatment was not protective on visual outcomes. CONCLUSIONS: A prophylactic LA treatment is necessary to protect from visual loss and retinal thinning in EAE-ON, suggesting that a clinical ON trial starting therapy after the onset of symptoms may not be successful.

Specific ion channels contribute to key elements of pathology during secondary degeneration following neurotrauma.

BACKGROUND: Following partial injury to the central nervous system, cells beyond the initial injury site undergo secondary degeneration, exacerbating loss of neurons, compact myelin and function. Changes in Ca2+ flux are associated with metabolic and structural changes, but it is not yet clear how flux through specific ion channels contributes to the various pathologies. Here, partial optic nerve transection in adult female rats was used to model secondary degeneration. Treatment with combinations of three ion channel inhibitors was used as a tool to investigate which elements of oxidative and structural damage related to long term functional outcomes. The inhibitors employed were the voltage gated Ca2+ channel inhibitor Lomerizine (Lom), the Ca2+ permeable AMPA receptor inhibitor YM872 and the P2X7 receptor inhibitor oxATP. RESULTS: Following partial optic nerve transection, hyper-phosphorylation of Tau and acetylated tubulin immunoreactivity were increased, and Nogo-A immunoreactivity was decreased, indicating that axonal changes occurred acutely. All combinations of ion channel inhibitors reduced hyper-phosphorylation of Tau and increased Nogo-A immunoreactivity at day 3 after injury. However, only Lom/oxATP or all three inhibitors in combination significantly reduced acetylated tubulin immunoreactivity. Most combinations of ion channel inhibitors were effective in restoring the lengths of the paranode and the paranodal gap, indicative of the length of the node of Ranvier, following injury. However, only all three inhibitors in combination restored to normal Ankyrin G length at the node of Ranvier. Similarly, HNE immunoreactivity and loss of oligodendrocyte precursor cells were only limited by treatment with all three ion channel inhibitors in combination. CONCLUSIONS: Data indicate that inhibiting any of a range of ion channels preserves certain elements of axon and node structure and limits some oxidative damage following injury, whereas ionic flux through all three channels must be inhibited to prevent lipid peroxidation and preserve Ankyrin G distribution and OPCs.

Pediatric Oculomotor Findings during Monocular Videonystagmography: A Developmental Study.

BACKGROUND: The differential diagnosis of a dizzy patient >4 yrs old is often aided by videonystagmography (VNG) testing to provide a global assessment of peripheral and central vestibular function. Although the value of a VNG evaluation is well-established, it remains unclear if the VNG test battery is as applicable to the pediatric population as it is for adults. Oculomotor testing specifically, as opposed to spontaneous, positional, and caloric testing, is dependent upon neurologic function. Thus, age and corresponding neuromaturation may have a significant effect on oculomotor findings. PURPOSE: The purpose of this investigation was to describe the effect of age on various tests of oculomotor function during a monocular VNG examination. Specifically, this study systematically characterized the impact of age on saccade tracking, smooth pursuit tracking, and optokinetic (OPK) nystagmus. RESEARCH DESIGN: The present study used a prospective, repeated measures design. STUDY SAMPLE: A total of 62 healthy participants were evaluated. Group 1 consisted of 29 4- to 6-yr-olds. Group 2 consisted of 33 21- to 44-yr-olds. Each participant completed a standard VNG oculomotor test battery including saccades, smooth pursuit, and OPK testing in randomized order using a commercially available system. DATA COLLECTION AND ANALYSIS: The response metrics saccade latency, accuracy, and speed, smooth pursuit gain, OPK nystagmus gain, speed and asymmetry ratios were collected and analyzed. RESULTS: Significant differences were noted between groups for saccade latency, smooth pursuit gain, and OPK asymmetry ratios. Saccade latency was significantly longer for the pediatric participants compared to the adult participants. Smooth pursuit gain was significantly less for the pediatric participants compared to the adult participants. The pediatric participants also demonstrated increased OPK asymmetry ratios compared to the adult participants. CONCLUSIONS: Significant differences were noted between the pediatric and adult participants for saccade latency, smooth pursuit gain, and OPK asymmetry. Saccade latency was significantly longer for the pediatric participants compared to the adult participants. Smooth pursuit gain was significantly less for the pediatric participants compared to the adult participants. The pediatric participants also demonstrated increased OPK asymmetry compared to the adult participants. Caution should be exercised when comparing pediatric test results to adult normative values to avoid "false positive" diagnoses of central vestibular involvement.

Neuromagnetic cortical activation during initiation of optokinetic nystagmus: an MEG pilot study.

PURPOSE: To investigate the spatiotemporal evolution of cortical activation during the initiation of optokinetic nystagmus using magnetoencephalography. BACKGROUND: Previous imaging studies of optokinetic nystagmus in humans using positron emission tomography and functional magnetic resonance imaging discovered activation of a large set of cortical and subcortical structures during steady-state optokinetic stimulation, but did not provide information on the temporal dynamics of the initial response. Imaging studies have shown that cortical areas responsible for vision in occipital and temporo-occipital areas are involved, i.e. cortical areas control optokinetic stimulation in humans. Magnetoencephalography provides measures that reflect neural ensemble activity in the millisecond time scale, allowing the identification of early cortical components of visuomotor integration. DESIGN/METHODS: We studied neuromagnetic cortical responses during the initiation of optokinetic nystagmus in 6 right-handed healthy subjects. Neuromagnetic activity was recorded with a whole-head magnetoencephalograph, consisting of 143 planar gradiometers. RESULTS: The mean (±SD) latency between stimulus onset and initiation of optokinetic nystagmus was 177.7 ± 59 ms. Initiation of optokinetic nystagmus evoked an early component in the primary visual cortex starting at 40-90 ms prior to the onset of the slow phase of nystagmus. Almost simultaneously an overlapping second component occurred bilaterally in the temporo-occipital area (visual motion areas), pronounced in the right hemisphere, starting at 10-60 ms prior to the slow-phase onset. Both components showed long-duration activity lasting for up to 100 ms after slow-phase onset. CONCLUSIONS: Our findings suggest that the initiation of optokinetic nystagmus induces early cortical activation in the occipital cortex and almost simultaneously bilaterally in the temporo-occipital cortex. These cortical regions might represent essential areas for the monitoring of retinal slip.

myosin 7aa(-/-) mutant zebrafish show mild photoreceptor degeneration and reduced electroretinographic responses.

Mutations in myosin VIIa (MYO7A) cause Usher Syndrome 1B (USH1B), a disease characterized by the combination of sensorineural hearing loss and visual impairment termed retinitis pigmentosa (RP). Although the shaker-1 mouse model of USH1B exists, only minor defects in the retina have been observed during its lifespan. Previous studies of the zebrafish mariner mutant, which also carries a mutation in myo7aa, revealed balance and hearing defects in the mutants but the retinal phenotype has not been described. We found elevated cell death in the outer nuclear layer (ONL) of myo7aa(-/-) mutants. While myo7aa(-/-) mutants retained visual behaviors in the optokinetic reflex (OKR) assay, electroretinogram (ERG) recordings revealed a significant decrease in both a- and b-wave amplitudes in mutant animals, but not a change in ERG threshold sensitivity. Immunohistochemistry showed mislocalization of rod and blue cone opsins and reduced expression of rod-specific markers in the myo7aa(-/-) ONL, providing further evidence that the photoreceptor degeneration observed represents the initial stages of the RP. Further, constant light exposure resulted in widespread photoreceptor degeneration and the appearance of large holes in the retinal pigment epithelium (RPE). No differences were observed in the retinomotor movements of the photoreceptors or in melanosome migration within the RPE, suggesting that myo7aa(-/-) does not function in these processes in teleosts. These results indicate that the zebrafish myo7aa(-/-) mutant is a useful animal model for the RP seen in humans with USH1B.

Differentiating cerebellopontine angle meningioma from schwannoma using caloric testing and vestibular-evoked myogenic potentials.

OBJECTIVE: This study utilized audiometry, and caloric, ocular vestibular-evoked myogenic potential (oVEMP) and cervical VEMP (cVEMP) tests to differentiate between cerebellopontine angle (CPA) meningioma and schwannoma. PATIENTS AND METHODS: Eleven CPA meningioma patients with mean tumor size 2.8±1.4 cm and another 11 CPA schwannoma patients with mean tumor size 2.7±1.0 cm were enrolled in this study. All patients underwent a battery of audiovestibular function tests. RESULTS: The two groups did not differ significantly in terms of clinical manifestation. The abnormal percentage of caloric test in the meningioma group was 36%, compared to 91% in the schwannoma group, and thus both groups differed significantly. However, such difference was not observed between the two groups regardless of mean hearing level, oVEMP test and cVEMP test. CONCLUSION: Combined caloric with oVEMP test results may help differentiate a CPA tumor. Correlation between the caloric and oVEMP test results in a CPA tumor indicates a schwannoma nature, while dissociation between the caloric and oVEMP test results depicts a meningioma character.

The effects of nicotine on cone and rod b-wave responses in larval zebrafish.

Acetylcholine is present in and released from starburst amacrine cells in the inner plexiform layer (IPL), but its role in retinal function except, perhaps, in early development, is unclear. Nicotinic acetylcholine receptors are thought to be present on ganglion, amacrine, and bipolar cell processes in the IPL, and it is known that acetylcholine increases the spontaneous and light-evoked responses of retinal ganglion cells. The effects of acetylcholine on bipolar cells are not known, and here we report the effects of nicotine on the b-wave of the electroretinogram in larval zebrafish. The b-wave originates mainly from ON-bipolar cells, and the larval zebrafish retina is cone-dominated. Only small rod responses can be elicited with dim lights in wild-type larval zebrafish retinas, but rod responses can be recorded over a range of intensities in a mutant ( n o optokinetic response f ) fi sh that has no cone function. We fi nd that nicotine strongly enhances cone-driven b-wave response amplitudes but depresses rod driven b-wave response amplitudes without, however, affecting rod- or cone-driven b-wave light sensitivity.

Accessing escalators: a central vestibular disorder after posterior fossa tumor removal.

About 20% of childhood tumors originate within the central nervous system. Progress in assessment and treatment of these lesions has led to improved survival rates. We describe a patient with a posterior fossa ependymoma who despite a remarkable recovery following treatment has been frustrated by difficulty in using escalators. Such symptom selectivity is explained by specific vertical visuomotor and high-frequency vestibular deficits disrupting the execution of this complex motor act.

Near infrared light reduces oxidative stress and preserves function in CNS tissue vulnerable to secondary degeneration following partial transection of the optic nerve.

Traumatic injury to the central nervous system (CNS) is accompanied by the spreading damage of secondary degeneration, resulting in further loss of neurons and function. Partial transection of the optic nerve (ON) has been used as a model of secondary degeneration, in which axons of retinal ganglion cells in the ventral ON are spared from initial dorsal injury, but are vulnerable to secondary degeneration. We have recently demonstrated that early after partial ON injury, oxidative stress spreads through the ventral ON vulnerable to secondary degeneration via astrocytes, and persists in the nerve in aggregates of cellular debris. In this study, we show that diffuse transcranial irradiation of the injury site with far red to near infrared (NIR) light (WARP 10 LED array, center wavelength 670 nm, irradiance 252 W/m(-2), 30 min exposure), as opposed to perception of light at this wavelength, reduced oxidative stress in areas of the ON vulnerable to secondary degeneration following partial injury. The WARP 10 NIR light treatment also prevented increases in NG-2-immunopositive oligodendrocyte precursor cells (OPCs) that occurred in ventral ON as a result of partial ON transection. Importantly, normal visual function was restored by NIR light treatment with the WARP 10 LED array, as assessed using optokinetic nystagmus and the Y-maze pattern discrimination task. To our knowledge, this is the first demonstration that 670-nm NIR light can reduce oxidative stress and improve function in the CNS following traumatic injury in vivo.

Topographical correlations of lateral medullary infarction with caloric- and vestibular-evoked myogenic potential results.

This study investigated the correlation of caloric- and vestibular-evoked myogenic potential (VEMP) results with topographical lesions of lateral medullary infarction. Five patients with lateral medullary infarction were enrolled in this study. Each patient underwent a battery of tests, including audiometry, caloric test, VEMP test, and magnetic resonance imaging (MRI) study. Gaze nystagmus was observed in four patients (80%), while abnormal pursuit, saccade, and optokinetic nystagmus tests were noted in all patients (100%). MRI demonstrated infarction at the ponto-medullary junction in one patient and upper medulla in one patient. Both patients revealed caloric areflexia and normal VEMPs. In contrast, another three patients with infarction at the middle inferior olive level, all displayed abnormal (including absent or delayed) VEMPs, and one patient showed caloric areflexia. Topographical correlations of lateral medullary infarction with caloric and VEMP tests reveal that caloric areflexia is possibly linked with rostrally located infarction, while absent or delayed VEMPs relate to caudally located infarction.

Channelrhodopsin-2 gene transduced into retinal ganglion cells restores functional vision in genetically blind rats.

To test the hypothesis that transduction of the channelrhodopsin-2 (ChR2) gene, a microbial-type rhodopsin gene, into retinal ganglion cells of genetically blind rats will restore functional vision, we recorded visually evoked potentials and tested the experimental rats for the presence of optomotor responses. The N-terminal fragment of the ChR2 gene was fused to the fluorescent protein Venus and inserted into an adeno-associated virus to make AAV2-ChR2V. AAV2-ChR2V was injected intravitreally into the eyes of 6-month-old dystrophic RCS (rdy/rdy) rats. Visual function was evaluated six weeks after the injection by recording visually evoked potentials (VEPs) and testing optomotor responses. The expression of ChR2V in the retina was investigated histologically. We found that VEPs could not be recorded from 6-month-old dystrophic RCS rats that had not been injected with AAV2-ChR2V. In contrast, VEPs were elicited from RCS rats six weeks after injection with AAV2-ChR2V. The VEPs were recorded at stimulation rates <20Hz, which was the same as that of normal rats. Optomotor responses were also significantly better after the AAV2-ChR2V injection. Expression of ChR2V was observed mainly in the retinal ganglion cells. These findings demonstrate that visual function can be restored in blind rats by transducing the ChR2V gene into retinal ganglion cells.

Oculomotricity parameters in digital nystagmography among children with and without learning disorders / Parâmetros de oculomotricidade à nistagmografia digital em crianças com e sem distúrbios de aprendizagem

The saccadic pathway involves numerous regions of the brain cortex, the cerebellum and the brainstem. Saccadic movement latency, velocity and precision parameters assess the efficacy of central nervous system (CNS) control over rapid eye movements. Very few disorders which alter the CNS are missed when these parameters are carefully measured using a computer. Pendular tracking assesses the integrity of the oculomotor system in controlling slow eye movements - vulnerable to CNS and vestibular system dysfunctions. Optokinetic nystagmus represents a stereoceptive response which compensates environment movements by psycho-optical inputs. AIMS: to compare the oculomotricity values found in children with and without learning complaints. MATERIALS AND METHODS: prospective study. We included in the study 28 children of both genders, within the age range between 8 and 12 years, with learning disorders (study group) and 15 without (control group). We carried out the fixed and randomized saccadic movement tests, pendular tracking study and optokinetic nystagmus. RESULTS: There was a statistically significant difference between the groups concerning the randomized saccadic movement velocity parameters and in the pendular tracking test. CONCLUSION: The children with learning disorders presented alterations in some oculomotricity tests when compared to children without complaints.

A via sacádica envolve várias regiões do córtex cerebral, cerebelo e tronco encefálico. Os parâmetros latência, velocidade e precisão dos movimentos sacádicos avaliam a eficiência do controle do sistema nervoso central (SNC) sobre os movimentos rápidos dos olhos. Poucas desordens que alteram o SNC deixam de ser detectadas quando esses parâmetros são medidos com rigor por meio de um computador. O rastreio pendular avalia a integridade do sistema oculomotor no controle dos movimentos oculares lentos, vulneráveis a disfunções do SNC e do sistema vestibular. O nistagmo optocinético representa uma resposta exteroceptiva que compensa os movimentos do meio ambiente por impulsos psico-ópticos. OBJETIVO: Comparar os valores da oculomotricidade encontrados em crianças com e sem queixas de aprendizagem. MATERIAL E MÉTODO: Estudo prospectivo. Foram incluídas no estudo 28 crianças, de ambos os gêneros, faixa etária de 8 a 12, anos com distúrbios de aprendizagem (grupo estudo) e 15 sem (grupo controle). Foram realizados os testes de movimentos sacádicos fixos e randomizados, pesquisa do rastreio pendular e nistagmo optocinético. RESULTADOS: Houve diferença estatisticamente significante entre os grupos nos parâmetros de velocidade dos movimentos sacádicos randomizados e na pesquisa do rastreio pendular. CONCLUSÃO: As crianças com distúrbios de aprendizagem apresentaram alterações em algumas provas de oculomotricidade quando comparadas com crianças sem queixas.

The commissural transfer of the horizontal optokinetic signal in the rat: a c-Fos study.

We applied the Fos method in rats subjected to horizontal optokinetic stimulation (OKS) to study whether optokinetic information is transferred through the commissural pretectal fibres from one optic tract nucleus (NOT) to the opposite. In binocular as well as in monocular nasalward OKS, the highest Fos immunoreactivity was found in the NOT contralateral to the nasalward stimulation, as expression of the activation either of direction-selective cells and of commissural neurons. Even the opposite NOT showed many Fos-positive cells activated by the opposite nucleus throughout the commissural pretectal pathway. They might be the GABA positive cells, which are thought to allow the activation in one nucleus to be transformed into inhibition of the opposite side. In monocular temporalward OKS, the inhibition on direction-selective cells and the consequent silencing of commissural neurons caused the faint immunoreactivity in the NOT contralateral to eye stimulated. In the opposite nucleus the few Fos-positive cells emerged as a consequence of the lack of the normal tonic commissurally mediated inhibition.

Electronystagmography in migraine equivalent syndrome.

OBJECTIVES: The aim of the study was to determine the efficacy of electronystagmography testing in the diagnosis of vertigo in children with migraine equivalent syndrome. STUDY DESIGN: The investigation included 20 children with "migraine equivalent syndrome" (group A), characterized by benign paroxysmal vertigo of childhood. As a control group, 50 healthy children were identified. SUBJECTS AND METHODS: All the subjects underwent rotatory vestibular stimulation by stop test, optokinetic stimulation, and simultaneous postrotatory vestibular and optokinetic stimulations (VVOR). RESULTS: For the analysis of the results, we considered nystagmus mean gain and direction of visual-vestibular-ocular-reflex (VVOR) nystagmus. In group A, all the children presented a VVOR nystagmus homodirectional to vestibular-ocular reflex (VOR). In the control group, all the subjects presented a VVOR nystagmus homodirectional to optokinetic nystagmus (OKN). CONCLUSION: In the healthy patients, VVOR nystagmus is always homodirectional to OKN and indicates the optokinetic system prevalence on VOR. The presence of a VVOR nystagmus homodirectional to VOR indicates the absence of the optokinetic system prevalence due to a central nervous system (CNS) modification and highlights a CNS disease. Our data highlight a possible correlation between CNS disorders and migraine equivalent syndrome.

Differentiation of PA from early PSP with different patterns of symptoms and CBF reduction.

OBJECTIVE: To clarify the features of pure akinesia (PA) and progressive supranuclear palsy (PSP) in the early stage of disease. METHODS: We investigated 15 PA and 41 PSP patients' clinical and radiologic features including head MRI, ethyl cysteinate dimmer-single photon emission-computed tomography (ECD-SPECT) and iodine-123 meta-iodobenzyl guanidine (123I-MIBG) myocardial scintigraphy. In ECD-SPECT study, cerebral blood flow (CBF) reduction was quantitatively expressed as Z-score, and that in the frontal lobe was evaluated. RESULTS: Many PSP patients claimed falls as the initial symptom but no PA patients did. Eye movement, as well as optokinetic nystagmus elicitation, was more frequently disturbed in PSP. Dementia, dysarthria and rigidity were also more frequent in PSP than in PA. Midbrain tegmentum atrophy in head MRI was more frequently observed in PSP. CBF in the frontal lobe, especially in the frontal eye field, was significantly lower in PSP than in PA. MIBG myocardial scintigraphy showed no difference between two groups. DISCUSSION: PA and PSP show distinct symptoms from the early stage, indicating that they are distinct disorders. The occurrence of falls and eye movement disturbance, as well as CBF reduction at the frontal eye field, is very important for distinguishing these disorders.

The effect of acute superior oblique palsy on torsional optokinetic nystagmus in monkeys.

PURPOSE: To investigate the effects of acquired superior oblique palsy (SOP) and corrective strabismus surgery on torsional optokinetic nystagmus (tOKN) in monkeys. METHODS: The trochlear nerve was severed intracranially in two rhesus monkeys (M1 and M2). For each monkey, more than 4 months after the SOP, the ipsilateral inferior oblique muscle was denervated and extirpated. For M2, 4 months later, the contralateral inferior rectus muscle was recessed by 2 mm. tOKN was elicited during monocular viewing of a rotating stimulus that was rear projected onto a screen 43.5 cm in front of the animal. Angular rotation of the stimulus about the center was 40 deg/s clockwise or counterclockwise. RESULTS: The main findings after trochlear nerve sectioning were (1) the amplitude and peak velocity of torsional quick and slow phases of the paretic eye was less than that in the normal eye for both intorsion and extorsion, and (2) the vertical motion of the paretic eye increased during both torsional slow and quick phases. After corrective inferior oblique surgery, both of these effects were even greater. CONCLUSIONS: Acquired SOP and corrective inferior oblique-weakening surgery create characteristic patterns of change in tOKN that reflect alterations in the dynamic properties of the extraocular muscles involved in eye torsion. tOKN also provides information complementary to that provided by the traditional Bielschowsky head-tilt test and potentially can help distinguish among different causes of vertical ocular misalignment.

Horizontal and vertical look and stare optokinetic nystagmus symmetry in healthy adult volunteers.

PURPOSE: Look optokinetic nystagmus (OKN) consists of voluntary tracking of details in a moving visual field, whereas stare OKN is reflexive and consists of shorter slow phases of lower gain. Horizontal OKN is symmetrical in healthy adults, whereas symmetry of vertical OKN is controversial. Horizontal and vertical look and stare OKN symmetry was measured, and the consistency of individual asymmetries and the effect of varying stimulus conditions were investigated. METHODS: Horizontal and vertical look and stare OKN gains were recorded in 15 healthy volunteers (40 degrees /s) using new methods to delineate look and stare OKN. Responses with right and left eye viewing were compared to investigate consistency of individual OKN asymmetry. In a second experiment, the symmetry of stare OKN was measured in nine volunteers varying velocity (20 degrees /s and 40 degrees /s), contrast (50% and 100%), grating contrast profile (square or sine wave), and stimulus shape (full screen or circular vignetted). RESULTS: There was no horizontal or vertical asymmetry in look or stare OKN gain for all volunteers grouped together. However, individual vertical asymmetries were strongly correlated for left and right eye viewing (look: r = 0.77, P = 0.0008; stare: r = 0.75, P = 0.001) and for look and stare OKN (r = 0.66, P = 7.3 x 10(-5)) because of a strong correlation for downward moving stimuli (r = 0.73, P = 0.002). Horizontal and vertical asymmetries were not significantly affected by variations in stimulus parameter. CONCLUSIONS: Although no horizontal or vertical OKN asymmetries existed for volunteers grouped together, vertical OKN was characterized by idiosyncratic asymmetries that remained consistent for an individual. Look and stare OKN gain is strongly associated for downward moving stimuli.