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.

Vestibular Function in Vestibular Schwannoma

Abstract Introduction: Traditionally vestibular function has been assessed using caloric irrigations; new methods have failed to reach the same level of accuracy. Vestibular nerve dysfunction occurs with ‘acoustic neuroma’ or ‘vestibular schwannoma. Quantitative testing of hearing by audiometry is much more widely available than quantitative vestibular testing, although consideration of vestibular dysfunction is part of clinical management. Validation of a new method of quantitative vestibular function testing could lead to more widespread integration into clinical practice and affect decision making (i.e. timing of surgery) Methods: A non-blind observational cohort study was undertaken in 31 participants. Study endpoints were either one or two separate participant measures in March/April 2013 the September/October 13. All participants underwent caloric and head impulse testing with video-oculography, while 10 underwent audiometric assessment. Repeat testing was performed for 10 subjects, including additional cognitive. The primary outcome was vestibular function test measures. Results: Video head impulse was strongly correlated with calorics (p=0.01) and showed good sensitivity (80%) and specificity (70%). Dizziness Handicap Inventory showed no correlation with other vestibular function measures. Participants showed reduced cognitive function tested using the CANTAB battery (p=0.01) Conclusion: Video head impulse testing is comparable to caloric testing to assess vestibular function. Vestibular lesions may lead to cognitive deficits. Further research is needed to better understand the role of video head impulse testing in vestibular schwannoma

Considerations for quantifying vestibular function

Vestibular dysfunction typically leads to disabling symptoms like dizziness, imbalance, and blurred vision during head movements. It affects up to 95 million adults in Europe and the USA. However, the diagnosis might be inconsistent due-to the lack of standardization of the vestibular tests. To improve the situation, this research quantified discrepancies in the outcomes of the main objective test caused by changing the methodology of testing and by different technical realizations. The effect of age in the tested population on the outcomes in the main functional test has also been studied. In addition, the existing test battery has been extended and the ways of analysis of data for patients fitted with the vestibular implant, a device that should restore the vestibular function as the cochlear implant restores hearing. The results of this PhD can facilitate standardization of the main vestibular tests, as well as to help improve evaluation of the impact of the vestibular implant

Incremental vestibulo-ocular reflex (VOR) adaptation In subjects with peripheral vestibular hypofunction

The vestibulo-ocular reflex (VOR) is the main retinal-image stabilizing mechanism during rapid (i.e. high-frequency content) head movements. When the peripheral vestibular system is impaired, i.e. vestibular hypofunction, through disease, trauma or the aging process, the VOR response is reduced resulting in retinal image slip. Subsequently, along with other vestibular conditions, the image of the world are blurred during head movements. In these conditions, vestibular information is less accurate and reliable, introducing perceptual uncertainty due to the sensory mismatch, leading to compromised balance, gait and ability to perform daily activities. Vestibular rehabilitation therapy (VRT) is a set of prescribed exercises that help improve function and reduce symptoms. The main pillar of VRT are gaze-stabilization exercises (GSE) which aim to improve the VOR response (by a process we call adaptation) or compensate for vestibular hypofunction by improving other related (lower-frequency operating) systems via substitution or habituation. To date, despite their acceptance in clinical guidelines, little evidence exists showing GSE improves the high-frequency VOR response using quantitative measures. Recently, the incremental VOR adaptation (IVA) technique has shown promising results, with marked VOR adaptation after as little as 15 minutes of training. However, these preliminary studies mostly looked at healthy subjects. The few IVA patient studies had small numbers, minimal follow up, and were not compared to conventional GSE or evaluated for clinical effect. In the following thesis, I sought to determine GSE training parameters for optimal VOR adaptation, as well as perform studies to compare short and long-term clinical outcomes after conventional GSE versus IVA training in patients with isolated vestibular hypofunction

Continuous Restoration of the Human Vestibulo-Ocular Reflex Using a Multichannel Vestibular Implant

Bilateral loss of vestibular sensation causes blurry vision during head movement, postural instability, chronic unsteadiness, and an increased fall risk. Individuals who fail to compensate despite rehabilitation therapy and cessation of exacerbating medications have no adequate treatment options. Inspired by the success of cochlear implants in restoring hearing, prosthetic stimulation of vestibular afferent neurons to encode head motion has been investigated as a potential treatment. Until now, no human had been continuously stimulated for more than a day, and human responses had not been assessed using 3-dimensional (3D) binocular oculography, without which one cannot determine whether an implant independently stimulates each of the implanted ear’s three semicircular canals. We report 3D binocular vestibulo-ocular reflex (VOR) responses in four human subjects with bilateral vestibular loss who were each implanted with a system designed to provide long-term motion-modulated prosthetic stimulation via electrodes in the semicircular canals of one ear. Initiation of prosthetic stimulation evoked nystagmus that decayed within 30 minutes. Stimulation targeting one canal produced 3D VOR responses aligned with that canal’s anatomic axis, while targeting canal pairs reliably yielded responses aligned with a vector sum of individual responses. Over 8 weeks of continuous use, modulated electrical stimulation produced robust and stable VOR responses that grew predictably with stimulus intensity and aligned approximately with any specified 3D head rotation axis. Combining mechanical and electrical stimulation enhanced low frequency responses. These results demonstrate that a vestibular implant can partially restore 3D inner ear sensation to individuals disabled by vestibular loss. Lastly, we show that temporal discretization inherent to cochlear implant signal processing has minimal effects on evoked responses, motivating a future combined device

Tracking the progress of peripheral Vestibular disease with the video Head Impulse Test

While the introduction of the video Head Impulse Test (vHIT) in 2009 revolutionized the diagnosis of vestibular disease, providing a measurement of the function of all six semicircular canals, this thesis aimed to determine the utility of tracking peripheral vestibular disease over time. Initial requirements were to analyze the factors affecting the quantitative output of the vHIT test and to develop practical techniques to ensure the output reflects the function of the tested canal. This included recognizing and avoiding artefacts, and an analysis of the interacting 3-D factors contributing to the 1-D output. Then, testing a cohort of normal subjects produced the age-matched range of normal vestibular ocular reflex (VOR) gain values for comparison against patient results. Subsequently, the vHIT and caloric responses of patients with Ménière's disease were examined, showing a dissociation between the tests. A thermo-fluid model was developed to explain this dissociation. Long-term vHIT tracking of a patient following sequential neuritis showed his peripheral function recovery took longer than expected, with a time constant of 150 days for the recovery of high-head-velocity horizontal responses. These results also suggested a way to tease out the relative contributions of peripheral gain change and central compensation to the patient’s overall functional VOR recovery. Finally, for patients requiring systemic gentamicin, the vHIT tracking data showed that early, often-repeated testing is necessary to detect the onset of vestibulo-toxic damage. If damage does occur, it is then necessary to continue vHIT tracking after the dosage regime has stopped, as function may continue to deteriorate. Thus, this thesis concluded unequivocally that tracking the progress of peripheral vestibular disease with correctly performed video Head Impulse Tests is both practical and extremely useful

Effects of oculomotor rehabilitation in children with visual and/or oculomotor dysfunction: a systematic review

A visão é essencial para o desenvolvimento das crianças, facilitando as suas habilidades cognitivas, sociais e motoras, e é importante, em especial, para o seu sucesso escolar. A presente revisão sistemática teve como objetivo estudar os efeitos da reabilitação oculomotora nas funções da visão e dos anexos do olho, e nas sensações associadas aos mesmos. Como objetivo secundário, foram estudados os efeitos da reabilitação oculomotora nas funções mentais de crianças com disfunções oculares. A pesquisa foi realizada nas bases de dados PubMed, Web of Science, Psychology and Behavioral Sciences Collection, Academic Search Complete e Scholar Google. Todos os estudos incluídos foram ensaios clínicos randomizados, cuja qualidade metodológica foi avaliada através da Physiotherapy Evidenced Database (PEDro) Scale. Dos nove estudos incluídos na síntese qualitativa, as amostras diziam respeito a crianças com insuficiência de convergência, ambliopia, Transtorno do Défice de Atenção e Hiperatividade, disfunção oculomotora, baixa habilidade de leitura e/ou hipermetropia. Todos os estudos demonstraram associação positiva entre o programa de reabilitação oculomotora em teste e a melhoria dos parâmetros visuais, oculomotores e/ou mentais, em crianças entre os 5 e os 17 anos de idade. Apesar do número de ameaças que colocam em causa as inferências destes achados, os resultados clínicos gerais sugerem que os programas de reabilitação oculomotora têm efeitos positivos nas funções da visão e dos anexos do olho e sensações associadas, bem como na cognição, comportamento e habilidades de leitura de crianças com disfunção oculomotora. São necessárias investigações adicionais para confirmar a eficácia da terapia oculomotora e para escolher o melhor programa de intervenção para cada paciente, dependendo dos objetivos de intervenção e das suas características clínicas e pessoais.Vision is essential to children development, facilitating cognitive, social and motor skills, and it is important, in particular, for school success. This systematic review aimed to study the effects of oculomotor rehabilitation on the functions of vision and structures adjoining the eye and on sensations associated, in children. As a secondary objective, the effects of oculomotor rehabilitation on the mental functions of children with ocular dysfunctions was studied. The research was conducted in PubMed, Web of Science, Psychology and Behavioral Sciences Collection, Academic Search Complete and Scholar Google databases. All the studies included were randomized controlled trials (RCT), which methodological quality was assessed with The Physiotherapy Evidence Database (PEDro) Scale. From the nine studies included in qualitative synthesis, the samples concerned children with convergence insufficiency, amblyopia, Attention Deficit Hyperactivity Disorder (ADHD), oculomotor dysfunction, poor reading skills, and/or hypermetropia. All of the studies demonstrated a positive association between the oculomotor rehabilitation program under test and improvement on visual, oculomotor and/or mental parameters, in children aged between 5 and 17 years old. Despite the number of threats that challenge the inferences of these findings, the overall clinical results suggest that oculomotor rehabilitation programs have positive effects on the functions of vision and structures adjoining the eye and sensations associated, as well as on cognition, behavior and reading skills of children with oculomotor dysfunction. Additional investigation is required to confirm the efficiency of oculomotor therapy and to choose the best intervention program to each patient, depending on the intervention objectives and their clinical and personal characteristics

Cerebellar Control of Saccades in Health and Disease

Vision is one of the senses that are used for gathering information about the surrounding environment. Patterns of light reflecting from the environment enter the eye and are projected onto the retina. The retina harbors photoreceptors, which transform the patterns of light into the electrical activity that neurons use to convey visual information. This information enables humans to observe and interact with the environment. To gather detailed visual information about the properties of an object of interest, it must be projected on the fovea. The fovea is the part of the retina that has the highest density of photoreceptors and therefore provides the highest visual acuity. The projection of (moving) objects can be kept on the fovea using smooth pursuit eye movements, and new objects can be targeted by using saccadic eye movements. Eye movements can be recorded and quantified with relative ease. Current technology enables us not only to record eye movements in healthy adults in a laboratory setting, but also in more challenging subjects such as children or patients, or to record concurrently with functional imaging in a MR-scanner. Eye movements can be studied at multiple levels, ranging from the quantification of reflexive behavior to the inference of cognitive strategies involved in voluntary eye movement control. With properly designed studies it is possible to assign a functional role to the different stages in the visuo-oculomotor pathways. These characteristics propelled a large number of electrophysiological and behavioral studies on eye movements in non-human primates and humans. Functional imaging studies during the last twenty years have opened new ways for further investigations of the oculomotor system. The accumulating knowledge from these electrophysiological, behavioral and the more recent imaging studies has led to a detailed, but not complete, understanding of the neuronal pathways that subserve the oculomotor system. This also led to the appreciation that eye movements exhibit specific abnormalities when a confined part of the nervous system that is involved in these eye movements is affected by disease or trauma. Therefore, eye movement abnormalities have a clear clinical value and can contribute to the diagnostic process in a clinical setting. This thesis focuses on the neuronal pathways and clinical use of saccadic and smooth pursuit eye movements