Diplopia and eye movement disorders.

Published versio

1D convolutional neural networks for detecting nystagmus

Vertigo is a type of dizziness characterised by the subjective feeling of movement despite being stationary. One in four individuals in the community experience symptoms of dizziness at any given time, and it can be challenging for clinicians to diagnose the underlying cause. When dizziness is the result of a malfunction in the inner-ear, the eyes flicker and this is called nystagmus. In this article we describe the first use of Deep Neural Network architectures applied to detecting nystagmus. The data used in these experiments was gathered during a clinical investigation of a novel medical device for recording head and eye movements. We describe methods for training networks using very limited amounts of training data, with an average of 11 mins of nystagmus across four subjects, and less than 24 hours of data in total, per subject. Our methods work by replicating and modifying existing samples to generate new data. In a cross-fold validation experiment, we achieve an average F1 score of 0.59 (SD = 0.24) across all four folds, showing that the methods employed are capable of identifying periods of nystagmus with a modest degree of accuracy. Notably, we were also able to identify periods of pathological nystagmus produced by a patient during an acute attack of Ménière's Disease, despite training the network on nystagmus that was induced by different means

Nystagmus as a Sign of Labyrinthine Disorders-Three-Dimensional Analysis of Nystagmus-

In order to diagnose the pathological condition of vertiginous patients, a detailed observation of nystagmus in addition to examination of body equilibrium and other neurotological tests are essential. How to precisely record the eye movements is one of the goals of the researchers and clinicians who are interested in the analysis of eye movements for a long time. For considering that, one has to think about the optimal method for recording eye movements. In this review, the author introduced a new method, that is, an analysis of vestibular induced eye movements in three-dimensions and discussed the advantages and limitations of this method

Evaluation of central and peripheral vestibular patients with the video-head impulse test

Dizziness and vertigo are highly prevalent symptoms that accompany a wide variety of conditions including peripheral vestibular dysfunction, central (vestibular) lesions and somatoform disorders. A correct diagnosis is the prerequisite for successful treatment, which should be directed towards the underlying pathophysiology. Neurophysiological methods that test the integrity of the peripheral and central vestibular system circuitry are essential to make an accurate diagnosis in clinical practice. Currently, that assessment is achieved primarily through eye movement analysis in response to semicircular canal stimulation, namely through caloric stimulation and head impulses. The quantification of the vestibulo-ocular reflex (VOR) dynamic parameters and the characterization of quick eye movements (QEM) triggered with head impulses can now be non-invasively and easily assessed with the video headimpulse test (vHIT). This provided a unique opportunity to carry out neurophysiological studies on the oculomotor responses generated by head impulses in humans. Our aim was to determine if the involvement of central vestibular pathways caused differential disturbances in VOR dynamic changes when explored with the vHIT, which could contribute not only to the differential diagnosis of patients but also to the understanding of VOR control mechanisms. We explored normal subjects and patients diagnosed with acute vestibular syndrome with spontaneous nystagmus of peripheral and central origin and hereditary neurodegenerative disorders. Looking for a simple sign of peripheral disease with the vHIT we noticed anti-compensatory eye movements (AQEM) in patients with peripheral aetiologies of spontaneous nystagmus (SN). In the first study we looked for the accuracy of AQEM to differentiate central from peripheral origins of SN. We recorded the eye movements in response to horizontal head impulses in a group of 43 consecutive patients with acute vestibular syndrome (12 with central, 31 with peripheral disorders), 5 patients after acute vestibular neurectomy (positive controls) and 39 healthy subjects (negative controls). AQEM were defined as quick eye movements (peak velocity above 50°/s) in the direction of the head movement. All patients with peripheral disorders and positive controls had AQEM (latency 231±53ms, amplitude 3.4±1.4º, velocity 166±55º/s) when their head was moved to the opposite side of the lesion. Central patients did not have AQEM. AQEM occurrence rate was higher in peripheral patients with contralesional (74±4%, mean±SD) in comparison to ipsilesional (1±4%) impulses (p<0.001). Overall diagnostic accuracy for differentiating central from peripheral patients was 96% (95% CI for AUC ROC curve: 0.90 to 1.0) for VOR gain and 100% (95% CI: 1.0 to 1.0) for AQEM occurrence rate. These results suggest that AQEM are a sign of vestibular imbalance in a peripheral deficit and should be added to VOR gain analysis in acute vestibular syndrome patients. In the second study on acute vestibular syndrome we reported on a patient with benign paroxysmal positional vertigo (BPPV) and spontaneous nystagmus due to otoconia causing a plug in the horizontal semicircular canal. The video head-impulse test revealed an eye velocity saturation with ipsilesional head impulses that normalized after liberatory maneuvers, documenting for the first time a reversible deficiency of the cupularendolymph high-frequency system dynamics. Furthermore cervical and ocular vestibular myogenic potentials were absent during stimulation of the affected side before the liberatory maneuvers, but normalized within 30 to 80 days. These observations challenge the common belief that VEMPs are evoked by otolith stimulation only, as the assumption of a reversible canal dysfunction by a plug offers a more plausible explanation for all effects. Finally, we reported on a patient presenting with a one-year history of progressive unsteadiness, particularly when in darkness. The video-Head Impulse Test (vHIT)1 (Figure 1 B) revealed a significantly reduced vestibuloocular reflex (VOR) gain in both horizontal (0.38±0.07 and 0.29±0.05) and posterior canals (0.49±0.05 and 0.38±0.06) with covert and overt corrective saccades, but normal VOR responses in both anterior canals (0.89±0.08 and 1.04±0.15), for right and left impulses, respectively. No plausible combination of end-organ lesion should be responsible for these observations. A brain MRI disclosed a left inferior cerebellar peduncle lesion suggestive of a glioma. To the best of our knowledge, this is the first report where three-dimensional vHIT, by means of peripheral-unlikely combinations of VOR lesion, has shown to be of topodiagnostic value. In the second set of studies we explored patients diagnosed with hereditary neurodegenerative disorders with and without vestibular system involvement. In the first study we explored 18 genetically confirmed Huntington’s disease patients (44.7±8.1 years; male=9). VOR latency, VOR gain and QEM characteristics were not different from controls (p>0.11 for all comparisons), suggesting that VOR is preserved at physiological frequency domains in these patients, even in more advanced stages of the disease. In the final study we explored 23 patients with a clinical and genetically confirmed diagnosis of spinocerebellar ataxia (SCA) type 3 (n=15), type 2 (n=4) and type 1 (n=4]), and 9 patients with early onset Friedreich’s ataxia (FA). VOR latency was higher in FA (p<0.001) and SCA3 (p=0.02) as compared to controls, discriminating FA from other ataxic patients with an overall diagnostic accuracy of 88%. VORr, VOR40 and VOR60 were significantly lower in FA and SCA3 (p<0.01). VOR80 was only significantly lower than controls in SCA3 (p<0.01), discriminating these from other ataxic patients with an overall diagnostic accuracy of 78%. Covert saccades were only triggered in SCA3 but with low occurrence rate and peak velocity (11.1±28.5% and 77.50±15.30°/s) whereas overt saccades were present in all groups. VORr gain showed a negative correlation with disease severity evaluated with SARA (Spearman r=-0.46, p=0.01). vHIT provides phenotypic information that differentiates the most common autosomal ataxias and can serve as a strategy to orient genetic diagnosis. A correlation between VOR and SARA raises the possibility of using VOR gain as a neurophysiologic biomarker for disease severity. Altogether these results supply relevant data in distinguishing peripheral and central nervous system (CNS) vestibular deficits, particularly acute deficits in emergency situation, as acute CNS vertigo can be life-threatening (stroke) and require immediate medical action. We first demonstrated that not only VOR instantaneous gain analysis has topodiagnostic value but also the analysis of gain dynamic changes, as these can point to individual aetiologies, e.g. a SCC plug. Secondly we demonstrated that quick eye movements also supply topodiagnostic cues, and should have their latency, peak velocity, direction and occurrence rate analysed. At a neurophysiological level, the oculomotor responses generated by head impulses also provide an understanding of both the biomechanical cupular-endolymph dynamics, the VOR dynamic control processes taking place and the modulation of vestibular spontaneous nystagmus with head impulsesA vertigem e a tontura são sintomas muito prevalentes que acompanham uma grande variedade de patologias, nomeadamente as vestibulopatias periféricas, centrais e as perturbações somatoformes. Um diagnóstico correcto é o pré-requisito para um tratamento eficaz, o qual deverá ser dirigido à patofisiologia de base. Os métodos neurofisiológicos que testam a integridade dos circuitos do sistema vestibular central e periférico são essenciais para alcançar um diagnóstico preciso na prática clínica. Actualmente, essa avaliação é realizada principalmente pela análise dos movimentos oculares originados pela estimulação dos canais semicirculares, nomeadamente a estimulação calórica e os impulsos cefálicos. A quantificação do parâmetros dinâmicos do reflexo vestíbulo-oculomotor (VOR) bem como a caracterização dos movimentos oculares rápidos (QEM, Quick Eye Movements) desencadeados com os impulsos cefálicos podem agora ser avaliados de forma fácil e nãoinvasiva com o vídeo Head Impulse Test (vHIT). Tal proporciona a oportunidade única de promover estudos neurofisiológicos das respostas oculomotoras desencadeadas pelos impulsos cefálicos em humanos. Acelerações horizontais da cabeça geram, na obscuridade, movimentos oculares conjugados lentos e compensatórios na direção oposta, sendo este reflexo denominado VOR. O principal objetivo deste reflexo é a manutenção de visão nítida e clara por estabilização da imagem na retina, principalmente durante os movimentos rápidos da cabeça. O Head Impulse Test (HIT)1 ou teste de impulsão cefálica é um teste clínico ativo em que este VOR angular é testado a alta frequência. O clínico, ao colocar-se de frente para o doente, aplica movimentos de frequência e direção imprevisíveis segundo o plano horizontal, de baixa amplitude (10-25º), alta aceleração (3.000-6.000º/s2) e velocidade (150-300º/s), enquanto o doente é instruído a manter a fixação num ponto. Se o VOR estiver intacto, o doente será capaz de manter a fixação, não se observando qualquer movimento rápido do olho, denominando-se o HIT de normal ou negativo. Pelo contrário, se o VOR não for compensatório, o olho acompanhará a cabeça durante a rotação impulsiva pelo que no final do impulso será necessário realizar uma sacada de refixação para recolocar o alvo 1 Halmagyi GM, Curthoys IS, Cremer PD, et al. The human horizontal vestibulo-ocular reflex in response to high-acceleration stimulation before and after unilateral vestibular neurectomy. Exp Brain Res. 1990;81(3):479–90. na fóvea, denominando-se o HIT de positivo ou patológico. Dado que não é possível ao olho humano detectar o movimento de fase lenta do VOR durante este impulso, a presença de uma sacada compensatória no final de um HIT clínico é entendida como um sinal indireto de uma fase lenta não compensatória. Enquanto o HIT unicamente permite a identificação da presença de sacadas após o impulso cefálico, o vídeo HIT (vHIT)2 possibilita não só a identificação e a quantificação da fase lenta do VOR, como também das fases rápidas geradas durante e após o impulso cefálico. Indivíduos saudáveis geram fases lentas compensatórias de baixa latência (7-10 ms), gerando fases rápidas ocasionais após os impulsos. Pelo contrário, doentes com lesão vestibular unilateral (UVL) desencadeiam fases lentas com latência aumentada, nãocompensatórias durante impulsos ipsilesionais , assim como movimentos oculares rápidos durante ou após os mesmos. Estes movimentos rápidos são conhecidos como sacadas covert se desencadeadas durante o impulso cefálico, dado a sua observação não ser possível a olho nu, ou como sacadas overt se desencadeadas após o impulso cefálico. Dado que estas fases rápidas apresentam o mesmo sentido da fase lenta deficitária, diminuindo o erro ocular, são consideradas sacadas compensatórias. Os doentes UVL agudos também podem gerar fases lentas não compensatórias durante os impulsos contralesionais, resultado da lesão da via inibitória ipsilesional, bem como gerar fases rápidas. A quantificação do HIT por vídeo-oculografia permite aumentar substancialmente a sensibilidade e a especificidade do HIT na avaliação do VOR sem as dificuldades técnicas dos coils, de difícil utilização na prática clínica. As novas câmaras digitais apresentam características de peso, forma, resolução espacial e de taxa de amostragem que permitem a sua utilização na prática clínica na quantificação do HIT com boas taxas de correlação com o coil . O registo dos perfis de velocidades ocular e cefálica durante o impulso cefálico permite o cálculo do ganho do VOR, definido como o ratio entre estas velocidades. Esse ratio pode ser calculado em momentos específicos, como p.ex. a 40, 60 e 80 ms após inicio do impulso (ganho instantâneo) ou como resultante de regressão linear (ganho por regressão). Enquanto que o último 2 Bartl K, Lehnen N, Kohlbecher S, Schneider E. Head Impulse Testing Using Videooculography. Ann N Y Acad Sci. 2009;1164(1):331–3.parece ser o valor mais robusto, o primeiro permite a avaliação variação dinâmica do ganho do VOR durante o impulso. Para o cálculo do VOR contribui a sua latência, de tal forma que se esta fosse zero deveríamos ter valores de ganho de 1.0 . Dada a existência de uma latência e, portanto, de uma discrepância entre as curvas de velocidades cefálica e ocular, os valores de normalização que obtivemos no nosso laboratório são ligeiramente inferiores (0.95±0.09). Calculando os limites de normalidade do ganho de VOR, obtivemos valores de 0.77 a 1.13. A avaliação do ganho de VOR permite por último o cálculo da assimetria interaural, que apresenta nas nossas séries, valores de normalidade muito baixos (<6.97%), quando comparados com os valores de normalidade para as provas calóricas (<25%). Os QEM são identificados como picos de aceleração bidirecionais e são classificados de acordo com o sentido relativo à fase lenta, a latência (ms), o pico de velocidade (º/s) e a taxa de ocorrência (%, taxa de impulsos que geram esses QEM). Os QEM podem apresentar o sentido da fase lenta do VOR deficitário e contribuir para a diminuição do erro ocular, sendo consideradas sacadas de correção ou sacadas catch-up, em analogia com os QEM da perseguição sacádica. Nas situações em que o ganho do VOR apresenta valores superiores à normalidade (situação observada em doentes com algumas patologias centrais) podem assumir o sentido contrário ao da fase lenta do VOR e ser igualmente classificadas como sacadas de correção uma vez que trazem a retina de regresso ao alvo. Nos indivíduos normais por nós estudados as sacadas overt apresentam valores de velocidade e de taxa de ocorrência relativamente baixos, enquanto as sacadas covert são inexistentes. Assim, a existência de uma lesão vestibular aguda (UVL) é verificável através do vHIT pela presença de uma fase lenta não compensatória durante os impulsos ipsilesionais. O cálculo do ganho do VOR e do índice de assimetria, permitem quantificar o grau da lesão. Nas fase aguda da lesão, o erro ocular resultante de um menor ganho de VOR é mais elevado, pelo que são identificadas sacadas compensatórias mais frequentes, com maior velocidade de pico e maior amplitude, tanto durante como após o impulso ipsilesional. Pelo contrário, durante a recuperação da fase lenta verifica-se o aumento progressivo da latência e diminuição da taxa de ocorrência destas sacadas. A maior parte dos doentes com síndrome vestibular agudo3 , definido como vertigem espontânea com nistagmo espontâneo, náuseas, vómitos e 3 Hotson JR, Baloh RW. Acute vestibular syndrome. N Engl J Med. 1998;339(10):680–5. desequilíbrio, resultam de lesão vestibular unilateral aguda. No entanto, a identificação no serviço de urgência daqueles que resultam de lesões do sistema nervoso central (CNS) e potencialmente em maior risco constitui um desafio. Como a análise isolada do tipo de nistagmo espontâneo não é suficiente para diferenciar os doentes com patologia periférica daqueles com patologia do sistema nervosa central, desenvolveram-se para este efeito algumas provas clínicas. Uma das mais importantes é o HIT. A ausência de sacada de refixação durante os impulsos ipsilesionais em doentes com nistagmo espontâneo e sem evidência de outros sinais e sintomas neurológicos, parece ser o que melhor prevê isoladamente a existência disfunção do CNS como causa do síndrome vestibular agudo4. A presença de nistagmo espontâneo constitui no entanto uma dificuldade adicional dado que as fases rápidas do nistagmo e a sacadas overt apresentam a mesma direção, ambas fazem o reset da fixação ocular e partilham propriedades cinemáticas. A realização de provas adicionais tais como o alinhamento ocular vertical (vertical skew) e sentido do nistagmo na levo e dextroversão aumentam o valor diagnóstico do HIT, mas requerem aptidões e competências habitualmente não disponíveis no serviço de urgência. Dado que o vHIT permite a quantificação das respostas oculomotoras aos estímulos impulsivos e apresenta uma curva de aprendizagem rápida na execução da prova, procurámos realizar um conjunto de experiências com o objetivo de determinar se o envolvimento de vias vestibulares centrais causam alterações do VOR dinâmico objectiváveis com o vHIT. Colocámos como hipótese que tais alterações poderiam ser não só traduzidas num algoritmo para topodiagnóstico clínico mas também contribuir para a compreensão dos mecanismos neurofisiológicos de controlo do VOR impulsivo. Para tal estudámos indivíduos saudáveis, doentes com UVL e nistagmo espontâneo de origem periférica e central e doentes com diagnósticos específicos de doença neurodegenerativa hereditária, com e sem envolvimento das vias vestibulares centrais. Nos próximos parágrafos são sumariamente descritos os fundamentos, objectivos, métodos, resultados e conclusões das experiências realizadas.

Vestibulo-Oculomotor Reflex Recording Using the Scleral Search Coil Technique. Review of Peripheral Vestibular Disorders

Our goal is to review vestibulo-oculomotor reflex (VOR) studies on several peripheral vestibular disorders (Ménière’s disease, vestibular neuritis, benign paroxysmal positional vertigo, superior canal dehiscence syndrome, and vestibular neuroma), using the scleral search coil (SSC) technique. Head movements are detected by vestibular receptors and the elicited VOR is responsible for compensatory 3 dimensional eye movements. Therefore, to study the VOR it is necessary to assess the direction and velocity of 3 dimensional head, and eye movements. This can be achieved using the SSC technique. Interaction between a scleral search coil and an alternating magnetic field generates an electrical signal that is proportional to eye position. Ideally, eye rotation axis is aligned with head rotation axis and VOR gain (eye velocity/head velocity) for horizontal and vertical head rotations is almost 1. The VOR gain, however, for torsional head rotations is smaller and about 0.

The role of non-invasive camera technology for gait analysis in patients with vestibular disorders

Purpose of the study Current balance assessments performed in clinical settings do not provide objective measurements of gait. Further, objective gait analysis typically requires expensive, large and dedicated laboratory facilities. The aim of this pilot study was to develop and assess a low-cost, non-invasive camera technology for gait analysis, to assist the clinical assessment of patients with vestibular disorders. Materials and methods used This is a prospective, case-controlled study that was developed jointly by the local Neurotology Department and the Centre for Sports Engineering Research. Eligible participants were approached and recruited at the local Neurotology Clinic. The gait assessment included two repetitions of a straight 7-metre walk. The gait analysis system, comprised of a camera (P3215-V, Axis Communications, Sweden) and analysis software was installed in an appropriately sized clinic room. Parameters extruded were walking velocity, step velocity, step length, cadence and step count per meter. The effect sizes (ESB) were calculated using the MatLab and were considered large, medium or small if >0.8, 0.5 and 0.2 respectively. This study was granted ethical approval by the Coventry and Warwickshire Research Ethics Committee (15/WM/0448). Results Six patients with vestibular dysfunction (P group) and six age-matched healthy volunteers (V group) were recruited in this study. The average velocity of gait for P group was 1189.1 ± 69.0 mm·s-1 whereas for V group it was 1351.4 ± 179.2 mm·s-1, (ESB: -0.91). The mean step velocities were 1353.1 ± 591.8 mm·s-1 and 1434.0 ± 396.5 mm·s-1 for P and V groups respectively (ESB: -0.20). The average cadence was 2.3 ± 0.9 Hz and 2.0 ± 0.5 Hz for P and V groups respectively (ESB: 0.60). The mean step length was 620.5 ± 150.7 mm for the P group and 728.5 ± 86.0 mm for the V group (ESB = -1.26). The average step count per meter was 1.7 ± 0.3 and 1.4 ± 0.1 for P and V groups respectively (ESB = 3.38). Conclusion This pilot study used a low-cost, non-invasive camera technology to identify changes in gait characteristics. Further, gait measurements were obtained without the application of markers or sensors to patients (i.e. non-invasive), thus allowing current, clinical practice to be supplemented by objective measurement, with minimal procedural impact. Further work needs to be undertaken to refine the device and produce normative data. In the future, similar technologies could be used in the community setting, providing an excellent diagnostic and monitoring tool for balance patients

A support system for the diagnosis of balance pathologies

Electronystagmography is one of the most widely used diagnostic studies for detecting balance dysfunction. There are various methods that can be used to carry out this diagnostic test, gyratory stimulation being the least invasive and most physiological for the patient. The procedure is based on measuring (analyzing) eye movements in search of certain patterns called nystagmuses. In this article, we introduce a hardware and software system for carrying out this type of studies that allows the healthcare professional to acquire, view, store, and manage results. The system also provides an intelligent method based on neural networks that can detect nystagmus patterns to help healthcare professionals make a diagnosis. The system is currently being used at a medical o ce for the detection of balance disorders. Even though there are similar systems that are commercially available, these are usually very expensive due to their hardware equipment requirements and use of proprietary technology. The system presented here was developed nationally at a very low cost and can be easily adapted to future changes in technology.VI Workshop Innovación en Sistemas de Software (WISS)Red de Universidades con Carreras en Informática (RedUNCI

A support system for the diagnosis of balance pathologies

Electronystagmography is one of the most widely used diagnostic studies for detecting balance dysfunction. There are various methods that can be used to carry out this diagnostic test, gyratory stimulation being the least invasive and most physiological for the patient. The procedure is based on measuring (analyzing) eye movements in search of certain patterns called nystagmuses. In this article, we introduce a hardware and software system for carrying out this type of studies that allows the healthcare professional to acquire, view, store, and manage results. The system also provides an intelligent method based on neural networks that can detect nystagmus patterns to help healthcare professionals make a diagnosis. The system is currently being used at a medical o ce for the detection of balance disorders. Even though there are similar systems that are commercially available, these are usually very expensive due to their hardware equipment requirements and use of proprietary technology. The system presented here was developed nationally at a very low cost and can be easily adapted to future changes in technology.VI Workshop Innovación en Sistemas de Software (WISS)Red de Universidades con Carreras en Informática (RedUNCI

Investigating nystagmus in patients with traumatic brain injury: A systematic review (1996 - 2016)

Background. Traumatic brain injury (TBI) is a health and socioeconomic concern worldwide. In patients with TBI, post-traumatic balance problems are often the result of damage to the vestibular system. Nystagmus is common in these patients, and can provide insight into the damage that has resulted from the trauma.Objective. To present a systematic overview of published literature regarding nystagmus in patients with TBI.Methods. Nine databases and platforms were searched during October 2016 for articles published between 1996 and 2016. Studies of any research design and published in English that focused on nystagmus in patients with TBI were considered for inclusion. A total of 110 articles were screened once duplicates had been removed, and 29 full-text articles were assessed. Eleven articles were included in the quality appraisal phase (using the McMaster tool), after which 10 articles were included in this review.Results. This review describes nystagmus in 713 patients, and all articles reviewed described the type of assessment method that was used. However, the results lacked comprehensive data regarding the assessment, measurement and description of nystagmus in TBI patients, or the possible link and relationship between nystagmus and TBI.Conclusions. This systematic review indicated that: (i) there is a growing body of evidence that benign paroxysmal positional vertigo should be considered during the medical examination of all patients suffering from head trauma; (ii) all patients with TBI should undergo visual (eye movement) and vestibular examination; and (iii) future studies should include quantitative measurements of eye movements and nystagmus.