The Audiologist’s Role in Assessment and Management of Mild Traumatic Brain Injuries

Mild Traumatic Brain Injuries (mTBI) are caused by a blow to the head and have many severe consequences from amnesia and loss of consciousness to cognitive symptoms such as fatigue, pain, dizziness, light and sound sensitivity, blurry vision, and may even have vestibular symptoms like vertigo secondary to the injury. The purpose of this doctoral scholarly project is to investigate the overlap of mTBIs and vestibular disorders to understand and emphasize how audiologists can be a valuable member of a multidisciplinary team to help assess and manage patients who experience traumatic brain injuries. Audiologists can play a key role in diagnosing vestibular disorders that may otherwise be overlooked due to overlap in mTBI symptoms. Audiologists may also be the best professional to help provide treatment options such as vestibular therapy to help patients heal from a mTBI. Recommendations for future directions are included for integrating audiologists into a multidisciplinary team for managing patients with mTBIs

MICRORNA-21 EXPRESSION IN VESTIBULAR SCHWANNOMA: POTENTIAL EFFECT ON GROWTH AND POSSIBLE PROGNOSTIC FACTOR

Background: Vestibular schwannomas are benign slow growing tumors arising from VIII cranial nerve. They are potential life threatening benign tumor because of intracranial located. The management could be surgical or conservative, but, left untreated, the tumor preserve the possibility to further growth and complication may arise. The natural history is however not predictable and prognostic factor to select patients manageable conservatively should be studied. The molecular pathways that lead to tumorigenesis and growth are not completely defined and a role could be played by microRNA. Elevated levels of microRNA-21 may contribute to tumor growth by deregulating the tumor suppressor phosphatase (PTEN) and consequent activation of protein kinase B (AKT). Aims: evaluation of microRNA-21 expression and measurement of PTEN levels in vestibular schwannoma specimens, compared with expression in normal nerve tissue, to assess a possible overexpression. A correlation of micorRNA-21 expression with tumor size and growth rate of the tumor, when available, was hypothesized to make a prognostic factor. Methods: collection of vestibular schwannomas and great auricular nerve specimens was done sterilely during surgery and immediately stored at -80°C, until its use. Quantitative real-time PCR was used to assess levels of expression of micro-RNA 21 and mRNA for PTEN. Levels of PTEN protein were assessed with immunohistochemical analysis. A retrospective correlation was done between data obtained and clinical notes of patients: tumor size and growth rate. Results: 31 patients with vestibular schwannoma were studied. MicroRNA-21 was founded overexpressed in all cases when compared with normal nerve tissue. Levels of microRNA-21 were not statistically related with tumor size at time of surgery, but a positive correlation with growth rate was noted in 10 cases in which this data was available. PTEN mRNA was founded in all cases. The PTEN protein levels were low in 10 specimens of 13 in which the data was available, and an inverse correlation with levels of microRNA-21 was noted. Conclusions: The microRNA-21 plays a role in tumor development and in growth regulation also in vestibular schwannoma. MicroRNA- 21 may be a proper molecular target for therapies act to reduce the tumor growth and could represent a prognostic factor in selecting patients manageable with observation or early hearing preservation surgery

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.

Anxiety and Related Disorders

Anxiety disorders are one of the most common psychiatric disorders worldwide and many aspects of anxiety can be observed. Anxious patients often consult primary care physicians for their treatment, but in most cases they do not accept the diagnosis of anxiety disorder. Anxiety is a symptom that could be seen in many organic disorders and can accompany almost any psychiatric disorder. Anxiety disorders are frequent and are associated with significant distress and dysfunction. Stigmatization is an important factor in insufficient diagnosis. The problems of anxiety cover all fields of life. This book intends to describe the epidemiological aspects and the main co-morbidities and consecutive diseases of the anxiety disorders

Hearing Disorders: Diagnosis, Management, and Future Opportunities

This book focuses on research on sensorineural hearing loss, syndromic or non-syndromic, related to genetic and viral factors. The metabolic syndrome, autoimmune etiopathogenesis, and new elements of cochlear implantation were also evaluated. New developments and utility of laboratory tests in inner ear diseases (sudden sensorineural hearing loss, Meniere disease, benign paroxysmal positional vertigo, vestibular neuritis) are also discussed

Handbook on clinical neurology and neurosurgery

HANDBOOKNEUROLOGYNEUROSURGERYКЛИНИЧЕСКАЯ НЕВРОЛОГИЯНЕВРОЛОГИЯНЕЙРОХИРУРГИЯThis handbook includes main parts of clinical neurology and neurosurgery

Balance disorder after traumatic brain injury : A multifactorial observational study.

This research was undertaken to improve the assessment and treatment of balance disorder after Traumatic Brain Injury (TBI). It had three aims: to identify factors that have shaped healthcare practice concerning balance disorder and describe barriers to improved practice&bull;; to develop understanding of the nature of TBI balance disorder; to establish proposals for an improved healthcare response for those with balance disorder following TBI. TBI is a significant cause of disability in the young adult population and problems with balance are consistently reported. A mixed methods approach was employed to address the aims within a common framework. This comprised a series of subject reviews, an observational study and a systematic analysis of emergent findings. Topics for the subject reviews were chosen for their relevance to TBI physiotherapy practice. The observational study involved 27 participants in the recovery and rehabilitation phase after TBI and was structured using a new comprehensive assessment protocol developed from first principles. Findings were explored using frequency analysis and thematic analysis generated from the development of individual participant narratives. Emergent topics were then considered with reference to the literature, existing theories and concepts of postural control. Different conceptualisations of balance were identified, influenced by discipline tradition, their evidence base, the evolution of ideas, and past and current purpose. Practice development was constrained by the lack of a comprehensive conceptualisation of human balance, inconsistent and fragmented service response and limited knowledge concerning the nature and prevalence of impairments affecting balance function after TBI. Balance disorder was found to be highly prevalent and multifactorial in nature. New sensorimotor characteristics of TBI balance disorder were identified, including observations of importance to the contentious debate concerning symptomatic minor TBI. Issues of key importance in the structure and process of assessment were also identified. Balance disorder is prevalent in the rehabilitation and recovery phase following TBI and is multifactorial in nature. Assessment and treatment of suspected balance disorder could be enhanced by the adoption of a single comprehensive conceptualisation of human balance, a systematic approach to assessment and formulation of causal hypotheses and a service process focused on the functional requirements of individuals. Research for the enhanced development of assessment and intervention strategies should also be pursued in the same context

Audiovestibular sensory processing in migraine

Migraine can be conceptualised as a disorder of sensory processing, manifest by such symptoms as headache (pain), phonophobia and photophobia. Current models of migraine pathophysiology incorporate a significant role for the brainstem. Vestibular migraine (VM) is a subtype of the disorder in which significant brainstem dysfunction has been documented. The condition is known to have a significant effect on mental health. This study was designed to investigate disturbances in audiovestibular brainstem function in vestibular migraine in a four part study: 1. Otoacoustic emission suppression by contralateral noise, a test of auditory efferent pathway function, was measured in a group of 33 VM patients and compared with 31 healthy controls. Regression analysis showed a higher rate of abnormality amongst the VM group (p=0.03). 2. Vestibular evoked myogenic potentials were recorded in a group of 30 VM patients and compared with 35 healthy controls. Recordings showed a higher rate of abnormal responses in the VM group than amongst controls (p=0.008). 3. The potential for vestibular stimuli to act as migraine triggers was investigated by observing the effect of vestibular testing or a control condition on 148 individuals. Vestibular stimulation was associated with a significant increase in the probability of developing a migraine attack over the following 24 hour period (p=0.01). 4. Psychological symptoms of depression and anxiety were assessed using questionnaires 39 patients with VM and compared with a control group of 44 patients with dizziness of other causes. Although the VM group had a significantly higher load of symptoms of depression and anxiety, regression modelling showed that this effect was largely accounted for by an excess of dizziness symptoms. In conclusion, this study documents a number of audiovestibular sensory processing abnormalities using a variety of techniques. Vestibular migraine has a significant effect on psychological wellbeing, largely via the associated balance symptoms