Genetic, morphological and electrophysiological findings in a patient with a rare pathogenic variant in the RS1 gene.

PURPOSE: In this study, we report a case of a young adult with X-linked juvenile retinoschisis (XLRS) with a rare pathogenic variant in the RS1 gene (c.522 + 2 T > A). METHODS: Ophthalmological evaluation, optical coherence tomography, full-field and multifocal electroretinograms and extensive genetic screening of genes related to visual loss were carried out in the participant. RESULTS: Clinical ophthalmological exams revealed a mild to moderate impairment of visual acuity. Retinal imaging showed bilateral foveal schisis, as well as normal a-wave, reduction in the b-wave amplitudes in dark- and light- adapted full-field electroretinograms, and abnormal oscillatory potentials. We found also diffuse amplitude reduction in multifocal electroretinogram arrays. A canonical splice variant was identified in the RS1 gene (c.522 + 2 T > A). CONCLUSION: A rare pathogenic variant of the RS1 gene was associated with diffuse retinal involvement (central and peripheral retina), probably in inner retina, and mild to moderate visual acuity impairment. The phenotypical characterization of rare mutations is relevant to provide information about the disease.

Peculiar aetiology for orbital apex syndrome: Wyburn-Mason syndrome as orbital apex lesion.

Background: Wyburn-Mason syndrome is a rare, non-hereditary congenital disease, belonging to the group of neurocutaneous syndromes with fewer than 100 cases reported since its first description in 1937. Case report: A young adult man was initially evaluated at the age of 2 years for proptosis and progressive visual impairment of the right eye, followed by impairment in ocular abduction, adduction and elevation as well as amaurosis. MRI revealed an expansive formation centred in the right orbit compromising conal spaces with distortion of eye muscles and optic nerve. The lesion extended through the superior orbital fissure into the right cavernous sinus and to the contralateral orbit. Despite embolisation, proptosis and oedema of the periorbital tissue continued to worsen. The combination of facial, ocular and intracranial vascular malformations and the exclusion of alternative aetiologies led to a diagnosis of cerebrofacial arteriovenous metameric syndrome (CAMS) 1 (Wyburn-Mason syndrome). Discussion: Important differential diagnoses are other CAMS, such as Sturge-Weber syndrome, as well as other conditions such as retinal cavernous haemangioma and vasoproliferative tumours. The optimal treatment regimen for severe cases of this syndrome is still unclear. Wyburn-Mason syndrome should be considered in patients presenting multiple arteriovenous malformations with orbital apex lesions.

Sarcoid optic neuropathy.

A 45-year-old woman presented with sudden complete vision loss in her left eye and retroorbital pain worsened by eye movements. A previous milder episode of vision loss had occurred in the same eye 1 year before, with complete recovery after high-dose intravenous methylprednisolone. She had no light perception in the left eye with a swollen optic disc, but with a normal right optic disc. There were no systemic manifestations or infections. MR scan of the brain showed extensive enlargement and enhancement of the left optic nerve and optic chiasm. After excluding infections and autoimmune markers, a left optic nerve biopsy confirmed non-caseating granulomas, leading to a diagnosis of neurosarcoidosis.

Eight-and-a-Half Syndrome Secondary to Neurotoxoplasmosis: A Rare Case Report.

Eight-and-a-half syndrome (EHS) is a neuro-ophthalmological condition characterised by horizontal gaze palsy, internuclear ophthalmoplegia, and ipsilateral facial palsy. Albeit rare, EHS is a well reported condition in the literature, with several reports presenting multiple aetiologies. Infarcts are the cause in more than half the cases. Human immunodeficiency virus (HIV)-related cases are rare, and are probably underreported in low- and middle-income countries. In this report, we describe EHS secondary to neurotoxoplasmosis in a 40-year-old HIV-positive Brazilian man. EHS secondary to neurotoxoplasmosis is a challenging diagnosis, with important differential diagnoses, notably for HIV patients.

Ocular contrapulsion followed by ipsipulsion in Wallenberg syndrome: The first case report in literature.

Wallenberg syndrome is also called lateral medullary syndrome, a neurological disorder resulting from occlusion of the vertebral artery or the posterior inferior cerebellar artery. The clinical presentations are associated with a variety of indications, including vestibulocerebellar symptoms, autonomic dysfunction and ipsilateral cerebellar signs. The ipsipulsion, an abnormality of the ocular movement associated with the Wallenberg syndrome, is more specific to the lateral medullary syndrome and is characterized by a tonic deviation of the eyes in the direction of the damaged side, more prominently when the visual fixation is interrupted. A 51-year-old male patient presented with a sudden permanent rotatory dizziness, unsteady gait, numbness in the left hemibody, left palate paresis, incoordination on left side and horizontal jerk nystagmus with left fast fase. Magnetic resonance imaging showed infarction in the left medulla and cerebellar. The ocular exam revealed saccadic lateropulsion ipsilateral to lesion. In the neurologic evaluation of the patient with Wallenberg syndrome, numerous abnormalities manifestations are present, such as vestibulo-ocular reflex deficiency, saccadic abnormalities, low pursuance movements and gaze fixation, and eye alignment dysfunction. This semiologic feature had not been described in literature until now. We hypothesize that an initial vasogenic edema extending to the left medial medulla following the acute stroke could explain the early presentation with saccadic counterpulsion. After one week and regression of the edema, the finding of lateropulsion has alternated to the classic ipsipulsion related to Wallenberg syndrome. The following case report depicts a rare case of Wallenberg syndrome associated with alterations of the ocular motricity.

Bedside video-ophthalmoscopy as an aid in the diagnosis of central vestibular syndromes.

The evaluation of central vestibular syndromes, especially in the acute setting, can pose a challenge even for the most experienced clinician. Of particular importance is the evaluation of ocular torsion and nystagmus, which can be sensitive for central vestibular pathology, but easily missed by the untrained eye. We present two cases of acute vestibular syndrome of central origin in which the use of magnified fundoscopy at the bedside aided the precise anatomical diagnosis to inform appropriate further management. We also review aspects of the pathophysiology and anatomy of vestibular roll plane disorders. In case 1, the finding of position-dependent ocular torsion facilitated a rapid distinction between central skew deviation and a trochlear nerve palsy. In case 2, the fundoscopic magnification identified a pure rotatory nystagmus indicative of a central vestibular disorder. Ophthalmoscopy remains a useful bedside technique in acute vertigo, but the use of inexpensive magnification with a smartphone can provide objective and recordable evidence of central vestibular pathology, aiding therapeutic decisions.

How does a small area cause big syndromes? A case report of a patient with one-and-a-half syndrome and MRI review of the anatomical pathways involved in causing different pontine neuro-ophthalmological syndromes.

PURPOSE: To describe the clinical symptoms, anatomical location of the injury and different etiologies of one-and-a-half syndrome and its variants. OBSERVATIONS: A small lesion to the brainstem can cause complex syndromes that involve the disfunction of different nuclei and pathways. A 52-year-old man presented with sudden onset of diplopia characterized by horizontal gaze palsy and internuclear ophthalmoplegia (INO). With these clinical characteristics, the patient was diagnosed with the one-and-a-half syndrome. Neuroimaging revealed an acute/subacute ischemic lacunar event in the pontine tegmentum. The one-and-a-half syndrome is described as a horizontal gaze palsy in one direction (damage to the paramedian pontine reticular formation [PPRF] or the VI nerve nucleus) and an internuclear ophthalmoplegia in the other direction (damage to the medial longitudinal fasciculus). Along with the traditional description, the closed anatomical proximity with other nuclei and pathways makes possible the appearance of other more complex syndromes that have been grouped as the one-and-a-half syndrome and its variants. CONCLUSIONS AND IMPORTANCE: A detailed clinical neuro-ophthalmologic examination, along with a clear understanding of the neuroanatomical pathways, gives clinicians a good diagnostic opportunity to determine the precise location of injuries to the brainstem.

Cohort profile: a collaborative multicentre study of retinal optical coherence tomography in 539 patients with neuromyelitis optica spectrum disorders (CROCTINO).

PURPOSE: Optical coherence tomography (OCT) captures retinal damage in neuromyelitis optica spectrum disorders (NMOSD). Previous studies investigating OCT in NMOSD have been limited by the rareness and heterogeneity of the disease. The goal of this study was to establish an image repository platform, which will facilitate neuroimaging studies in NMOSD. Here we summarise the profile of the Collaborative OCT in NMOSD repository as the initial effort in establishing this platform. This repository should prove invaluable for studies using OCT to investigate NMOSD. PARTICIPANTS: The current cohort includes data from 539 patients with NMOSD and 114 healthy controls. These were collected at 22 participating centres from North and South America, Asia and Europe. The dataset consists of demographic details, diagnosis, antibody status, clinical disability, visual function, history of optic neuritis and other NMOSD defining attacks, and OCT source data from three different OCT devices. FINDINGS TO DATE: The cohort informs similar demographic and clinical characteristics as those of previously published NMOSD cohorts. The image repository platform and centre network continue to be available for future prospective neuroimaging studies in NMOSD. For the conduct of the study, we have refined OCT image quality criteria and developed a cross-device intraretinal segmentation pipeline. FUTURE PLANS: We are pursuing several scientific projects based on the repository, such as analysing retinal layer thickness measurements, in this cohort in an attempt to identify differences between distinct disease phenotypes, demographics and ethnicities. The dataset will be available for further projects to interested, qualified parties, such as those using specialised image analysis or artificial intelligence applications.

Paquimeningitis relacionada con IgG4 y la visión. Reporte de caso / Ophthalmological manifestations of IgG4-related pachymeningitis. A case repor

Introducción: la inmunoglobulina G4 es un subtipo de inmunoglobulina G que corresponde a menos del 5% del total de inmunoglo-bulinas. Niveles elevados de esta molécula se han asociado con el desarrollo de diferentes patologías. Método: presentación de caso clínico. Resultados: se presenta el caso de una mujer de 51 años que consultó por disminución de agudeza visual, escotoma central en ojo izquierdo y edema de papila bilateral. Se encontraron signos compatibles con paquimeningitis en la resonancia nuclear magnética. También presentó aumento de presión de apertura en la punción lumbar. En el estudio de laboratorio se observó un aumento en los niveles plasmáticos de IgG4, lo cual llevó al diagnóstico de paquimeningitis relacionada con IgG4. La paciente fue tratada con corticoides y azatioprina, con excelente evolución posterior al normalizar agudeza visual y campos visuales. Conclusión: en este artículo se describen tres elementos importantes a considerar en estos pacientes: pérdida de visión, edema de discos ópticos y cambios en campo visual.

Introduction: G4 immunoglobulin is 5% of total immunoglobulins in plasma. Elevated levels of this protein are associated with several diseases. Methods: clinical case report. Results: we report a case of a 51-year-old woman who presented with loss of vision, a central scotoma over her left eye and bilateral optic disc edema. She had findings compatible with pachymeningitis based on magnetic resonance imaging. She also exhibited an increased opening pressure in lumbar puncture. In the laboratory workup, we found a two-fold increase in IgG4 levels, which led to a diagnosis of pachymeningitis related to IgG4. The patient was treated accordingly with corticosteroids and azathioprine. The patient experienced excellent progression with complete recovery of her visual acuity and normalization of the visual fields. Conclusion: there is three elements to consider in these patients: vision loss, optic disc edema and visual field changes.

Neurophthalmological conditions mimicking glaucomatous optic neuropathy: analysis of the most common causes of misdiagnosis.

BACKGROUND: To analyze the most common neurophthalmological conditions that may mimic glaucomatous optic neuropathy and to determine which most often lead to misdiagnosis when evaluated by a glaucoma specialist. METHODS: We reviewed the charts of consecutive patients with optic neuropathies caused by neurophthalmological conditions screened in a single Eye Clinic within a period of 24 months. Within these enrolled patients, we selected the eyes whose fundoscopic appearance could resemble glaucoma based in pre-defined criteria (vertical cup-to-disc ratio ≥0.6, asymmetry of the cup-to-disc ratio ≥0.2 between eyes, presence of localized retinal nerve fiber layer and/or neuroretinal rim defects, and disc haemorrhages). Then, color fundus photographs and Humphrey Visual Field tests (HVF) of these eyes were mixed with tests from 21 consecutive glaucomatous patients (42 eyes with normal tension glaucoma). These images were mixed randomly and a masked glaucoma specialist was asked to distinguish if each set of exams was from a patient with glaucoma or with a neurophthalmologic condition. RESULTS: Among the 101 eyes (68 patients) enrolled with neurophthalmological diseases, 16 (15.8%) were classified as conditions that could mimic glaucoma. The most common diagnoses were ischemic optic neuropathy (25%), compressive optic neuropathy (18.7%) and hereditary optic neuropathy (18.7%). Based on the analysis of fundus photographs and HVF tests, 25% of these were misdiagnosed as glaucoma (two ischemic optic neuropathies and two congenital optic disc anomalies). Conversely, 11.9% of the glaucomatous neuropathies were misdiagnosed as neurophthalmological disorders. Overall, the glaucoma specialist correctly diagnosed 84.5% of the eyes. CONCLUSIONS: Some neurophthalmological disorders can mimic glaucoma. In our study, isquemic and compressive optic neuropathies were the ones that most often did so. Almost one quarter of the eyes were misdiagnosed when evaluated by a glaucoma specialist, which can lead to inadequate management and influence the prognosis of these patients.

Manifestaciones neuroftalmológicas en la enfermedad de Parkinson / Neurophthalmologic manifestations of Parkinson´s disease

La enfermedad de Parkinson es un desorden neurodegenerativo progresivo provocado por un déficit de dopamina que desencadena importantes alteraciones motoras y no motoras. Dentro de estas, un considerable grupo constituye motivo de interés para el neuroftalmólogo. La enfermedad ha sido siempre más reconocida por sus alteraciones motoras. El objetivo fundamental de esta revisión es hacer énfasis en el diagnóstico de las afectaciones visuales en la enfermedad de Parkinson y de esta forma mejorar en lo posible la calidad de vida de los pacientes. Se realizó una amplia búsqueda en PUBMED y se revisaron 60 artículos relacionados con el tema, publicados entre los años 1984 y 2012

Parkinson's disease is a progressive neurodegenerative disorder caused by a dopamine deficit that triggers important motor and non-motor alterations. A large group of them attracts the interest of the neurophthalmologists. This disease has always been more recognized by its motor alterations. The main objective of this review was to make emphasis on the diagnosis of visual disorders in Parkinson's disease patients and thus to improve their quality of life. An extensive search was made in PUBMED where 60 articles on this topic, published from 1984 to 2012, were reviewed

Veinticinco años de la Unidad de Neuro-oftalmología del Hospital Vargas de Caracas (1980-2005): apuntes para una biografía / Twenty five years of the Neuro-ophtalmologic Unit in the Vargas Hospital in Caracas (1980-2005)

Con la Unidad de Neuro-oftalmología del Hospital Vargas de Caracas se inicia en Venezuela el estudio de condiciones que afectan el órgano de la visión y sus relaciones con el sistema nervioso central. Fundada en 1980 con una idea asistencial-docente, se ha mantenido activa por más de 25 años y es única en su género en el país. Ha sustentado su ser y hacer en cuatro principios fundamentales, asistecia, docencia, investigación clínica y extensión. Asiste a enfermos del hospital y procedentes de diversos centros de la capital, así como también del interior del país, mediante una consulta externa gratuita muy activa en la cual se evalúan diariamente cerca de 16 pacientes de consulta sucesiva y 4 de primera de consulta. Luego y sobre la base de una experiencia clínica, progresó hacia la docencia de posgrado recibiendo por cortos períodos cerca de 40 pasantes por año entre oftalmólogos, neurológos y neuropediatras; adicionalmente se aceptan médicos especialistas para programa de "fellowship" en Neuro-Oftalmología de un año de duración. De esta manera han egresado 32 fellows, 24 venezolanos y 8 extranjeros: 26 oftalmológos, 3 neurólogos y médicos internistas. Con base en muestras de pacientes atendidos a lo largo de los años, se realiza investigación clínica continua de problemas neuro-oftalmológicos, lo cual ha permitido evaluar y desempeñar las diferencias regionales de algunas condiciones clínicas que adoptan características diferentes a otras latitudes. Porteriormente ha extendido su influencia extramuros con asistencia de su personal a otros hospitales para dictar cursos, charlas y ejercicios clínicos con pacientes, y en congresos y cursos internacionales

The systematic study of the conditions that affect the visual organ and its relations with the central nervous system began in this country with the Neuro-Ophthalmology Unit of the Vargas Hospital in Caracas, ascribed to the Department of Clinical Medicine “B” of the “José María Vargas” Medical School, attached to the Faculty of Medicine of the Central University of Venezuela. Founded in 1980 as a teaching clinic, the unit has stayed active for more than 25 years and is unique in its field. It has maintained its place based on four fundamental principles: assistance, education, clinical research and expansion. It treats patients from the Vargas Hospital and from other centers of the country, through an active external consultation scheme, free of charge, in which close to 16 follow-up patients and 4 first-time patients are tended to daily. Subsequently, based on extensive clinical experience, the Unit progressed in to post-graduate education, receiving close to 40 residents from ophthalmology, neurology and neuro-pediatrics programs each year for short periods for direct and supervised teaching. Additionally, especialists have been accepted for a one-year “fellowship” program in Neuro-Ophthalmology. Thirty-two fellows (24 Venezuelans and 8 foreigners) have graduated from this program: 26 ophthalmologists, 3 neurologists and 4 internists, many of which will assume taching duties in their own countries. Over the years, based on a sample of treated patients, continued clinical research of neuro-ophthalmologic problems is undertaken, which has allowed the evaluation, unraveling and publishing of the regional differences of certain clinical conditions. Subsequently, with the assistance of its personnel, the Unit has expanded its influence to other hospitals as well as national and international institutions, running courses and lectures and conducting clinical exercises with patients

Historia de la neurooftalmología / History of Neuroophthalmology

Se hace una introducción para explicar la dedicación de este número de la Revista Cubana de Oftalmología a la Neurooftalmología y se expone su desarrollo tomando en consideración los estudios de los elementos anatómicos y fisiológicos que constituyen su base, técnicas de exploración y las personalidades e instituciones, que a través de los años, en el mundo, y en Cuba, han contribuido a su desarrollo.

An introduction is made to explain why this issue of the Revista Cubana de Oftalmología is devoted to Neuroophthalmology. Its development is exposed taking into consideration the studies of the anatomical and physiological elements that constitute its basis, the exploratory techniques and the personalities and institutions that through the years have contributed to its development in Cuba and in the world.