Towards an explanation for 'unexplained' dizziness in older people.

BACKGROUND: Subjective unsteadiness or dizziness, usually without increase in body sway, is common in older people. The absence of mechanistic understanding of such symptoms renders clinical management difficult. Here, we explore the mechanisms behind such idiopathic dizziness (ID), focusing on postural control abnormalities. METHODS: Thirty patients with ID and 30 age-matched controls stood on a moving platform. Platform oscillations were randomly delivered at different velocities (from 0 to 0.2 m/s). Markers of postural control, including objective sway (trunk sway path, recorded via a sensor attached to vertebrae C7), stepping responses, subjective instability and anxiety ratings were obtained. MRI scans were available for correlations with levels of cerebral small vessel disease in 28 patients and 24 controls. RESULTS: We observed a significant relationship between objective and subjective instability in all groups. The slope of this fit was significantly steeper for patients than controls, indicating greater perceived instability for the same body sway. Stepwise linear regression showed that the slopes of this objective-subjective instability relationship were best explained by concerns about falling (Falls Efficacy Scale-International), clinical physical functioning (Short Physical Performance Battery) and, to some degree, by neuroimaging markers of cerebral small vessel disease. In addition, patients had a reduced stepping threshold, suggesting an overly cautious postural response. CONCLUSION: The distorted perception of instability and subtle impairments in balance control, including abnormal and overly cautious stepping responses, underlies the emergence of ID. It appears to relate to changes in postural performance, psychological functioning and disruption of postural brain networks associated with cerebral small vessel disease.

Hearing rehabilitation of adults with auditory processing disorder: a systematic review and meta-analysis of current evidence-based interventions.

Background: For adults with auditory processing disorder (APD), listening and communicating can be difficult, potentially leading to social isolation, depression, employment difficulties and certainly reducing the quality of life. Despite existing practice guidelines suggesting treatments, the efficacy of these interventions remains uncertain due to a lack of comprehensive reviews. This systematic review and meta-analysis aim to establish current evidence on the effectiveness of interventions for APD in adults, addressing the urgent need for clarity in the field. Methods: Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic search across MEDLINE (Ovid), Embase (Ovid), Web of Science and Scopus, focusing on intervention studies involving adults with APD. Studies that met the inclusion criteria were grouped according to intervention with a meta-analysis only conducted where intervention, study design and outcome measure were comparable. Results: Out of 1,618 screened records, 13 studies were included, covering auditory training (AT), low-gain hearing aids (LGHA), and personal remote microphone systems (PRMS). Our analysis revealed: AT, Mixed results with some improvements in speech intelligibility and listening ability, indicating potential benefits but highlighting the need for standardized protocols; LGHA, The included studies demonstrated significant improvements in monaural low redundancy speech testing (p < 0.05), suggesting LGHA could enhance speech perception in noisy environments. However, limitations include small sample sizes and potential biases in study design. PRMS, Demonstrated the most consistent evidence of benefit, significantly improving speech testing results, with no additional benefit from combining PRMS with other interventions. Discussion: PRMS presents the most evidence-supported intervention for adults with APD, although further high-quality research is crucial for all intervention types. The establishment and implementation of standardized intervention protocols alongside rigorously validated outcome measures will enable a more evidence-based approach to managing APD in adults.

Acceptability of Audiovestibular Assessment in the Home-A Patient Survey.

The COVID-19 pandemic dramatically changed health service delivery with vulnerable patients advised to isolate and appointments provided virtually. This change affected recruitment into an observational cohort study, undertaken at a single site, where participants with mitochondrial disorders were due to have specialist hospital-based audiovestibular tests. To ensure study viability, the study protocol was amended to allow home-based assessment for vulnerable participants. Here, we report outcomes of an online survey of participants who underwent home-based assessment, related to the experience, perceived benefits, and drawbacks of home audiovestibular assessments. Seventeen participants underwent home-based neuro-otological assessment, due to the need to isolate during COVID-19. Following the assessment, 16 out of 17 participants completed an anonymised online survey to share their experiences of the specialist home-based assessment. One hundred percent of participants rated the home-based assessment 'very positively' and would recommend it to others. Sixty-three percent rated it better than attending hospital outpatient testing settings. The benefits included no travel burden (27%) and reduced stress (13%). A majority reported no drawbacks in having the home visit. The patient-reported feedback suggests a person-centred approach where audiovestibular assessments are conducted in their homes is feasible for patients, acceptable and seen as beneficial to a vulnerable group of patients.

Exploring Inner Ear and Brain Connectivity through Perilymph Sampling for Early Detection of Neurological Diseases: A Provocative Proposal.

Recent evidence shows that it is possible to identify the elements responsible for sensorineural hearing loss, such as pro-inflammatory cytokines and macrophages, by performing perilymph sampling. However, current studies have only focused on the diagnosis of such as otologic conditions. Hearing loss is a feature of certain neuroinflammatory disorders such as multiple sclerosis, and sensorineural hearing loss (SNHL) is widely detected in Alzheimer's disease. Although the environment of the inner ear is highly regulated, there are several communication pathways between the perilymph of the inner ear and cerebrospinal fluid (CSF). Thus, examination of the perilymph may help understand the mechanism behind the hearing loss observed in certain neuroinflammatory and neurodegenerative diseases. Herein, we review the constituents of CSF and perilymph, the anatomy of the inner ear and its connection with the brain. Then, we discuss the relevance of perilymph sampling in neurology. Currently, perilymph sampling is only performed during surgical procedures, but we hypothesize a simplified and low-invasive technique that could allow sampling in a clinical setting with the same ease as performing an intratympanic injection under direct visual check. The use of this modified technique could allow for perilymph sampling in people with hearing loss and neuroinflammatory/neurodegenerative disorders and clarify the relationship between these conditions; in fact, by measuring the concentration of neuroinflammatory and/or neurodegenerative biomarkers and those typically expressed in the inner ear in aging SNHL, it could be possible to understand if SNHL is caused by aging or neuroinflammation.

Introduction to the assessment and management of persistent postural-perceptual dizziness.

OBJECTIVE: Persistent postural-perceptual dizziness classifies patients with chronic dizziness, often triggered by an acute episode of vestibular dysfunction or threat to balance. Unsteadiness and spatial disorientation vary in intensity but persist for over three months, exacerbated by complex visual environments. METHOD: Literature suggests diagnosis relies on a clinical history of persistent subjective dizziness and normal vestibular and neurological examination findings. Behavioural diagnostic biomarkers have been proposed, to facilitate diagnosis. RESULTS: Research has focused on understanding the neural mechanisms that underpin this perceptual disorder, with imaging data supporting altered connectivity between neural brain networks that process vision, motion and emotion. Behavioural research identified the perceptual and motor responses to a heightened perception of imbalance. CONCLUSION: Management utilises head and body motion detection, and downregulation of visual motion excitability, reducing postural hypervigilance and anxiety. Combinations of physical and cognitive therapies, with antidepressant medications, help if the condition is associated with mood disorder.

Digital biomarkers from gaze tests for classification of central and peripheral lesions in acute vestibular syndrome.

Acute vestibular syndrome (AVS) is characterised by a sudden vertigo, gait instability, nausea and nystagmus. Accurate and rapid triage of patients with AVS to differentiate central (potentially sinister) from peripheral (usually benign) root causes is a challenge faced across emergency medicine settings. While there exist bedside exams which can reliably differentiate serious cases, they are underused due to clinicians' general unfamiliarity and low confidence interpreting results. Nystagmus is a fundamental part of AVS and can facilitate triaging, but identification of relevant characteristics requires expertise. This work presents two quantitative digital biomarkers from nystagmus analysis, which capture diagnostically-relevant information. The directionality biomarker evaluates changes in direction to differentiate spontaneous and gaze-evoked (direction-changing) nystagmus, while the intensity differential biomarker describes changes in intensity across eccentric gaze tests. In order to evaluate biomarkers, 24 sets of three gaze tests (left, right, and primary) are analysed. Both novel biomarkers were found to perform well, particularly directionality which was a perfect classifier. Generally, the biomarkers matched or eclipsed the performance of quantitative nystagmus features found in the literature. They also surpassed the performance of a support vector machine classifier trained on the same dataset, which achieved an accuracy of 75%. In conclusion, these biomarkers simplify the diagnostic process for non-specialist clinicians, bridging the gap between emergency care and specialist evaluation, ultimately benefiting patients with AVS.

Detecting Abnormal Eye Movements in Patients with Neurodegenerative Diseases - Current Insights.

This review delineates the ocular motor disturbances across a spectrum of neurodegenerative disorders, including Alzheimer's Disease (AD) and related disorders (ADRD), Parkinson's Disease (PD), atypical parkinsonism, and others, leveraging advancements in eye-tracking technology for enhanced diagnostic precision. We delve into the different classes of eye movements, their clinical assessment, and specific abnormalities manifesting in these diseases, highlighting the nuanced differences and shared patterns. For instance, AD and ADRD are characterized by increased saccadic latencies and instability in fixation, while PD features saccadic hypometria and mild smooth pursuit impairments. Atypical parkinsonism, notably Progressive Supranuclear Palsy (PSP) and Corticobasal Syndrome (CBS), presents with distinct ocular motor signatures such as vertical supranuclear gaze palsy and saccadic apraxia, respectively. Our review underscores the diagnostic value of eye movement analysis in differentiating between these disorders and also posits the existence of underlying common pathological mechanisms. We discuss how eye movements have potential as biomarkers for neurodegenerative diseases but also some of the existing limitations.

Lesion network of oculogyric crises maps to brain dopaminergic transcriptomic signature.

Oculogyric crises are acute episodes of sustained, typically upward, conjugate deviation of the eyes. Oculogyric crises usually occur as the result of acute D2-dopamine receptor blockade, but the brain areas causally involved in generating this symptom remain elusive. Here, we used data from 14 previously reported cases of lesion-induced oculogyric crises and employed lesion network mapping to identify their shared connections throughout the brain. This analysis yielded a common network that included basal ganglia, thalamic and brainstem nuclei, as well as the cerebellum. Comparison of this network with gene expression profiles associated with the dopamine system revealed spatial overlap specifically with the gene coding for dopamine receptor type 2 (DRD2), as defined by a large-scale transcriptomic database of the human brain. Furthermore, spatial overlap with DRD2 and DRD3 gene expression was specific to brain lesions associated with oculogyric crises when contrasted to lesions that led to other movement disorders. Our findings identify a common neural network causally involved in the occurrence of oculogyric crises and provide a pathophysiological link between lesion locations causing this syndrome and its most common pharmacological cause, namely DRD2 blockade.

A diagnostic framework to identify vestibular involvement in multi-sensory neurological disease.

BACKGROUND AND PURPOSE: Identifying vestibular causes of dizziness and unsteadiness in multi-sensory neurological disease can be challenging, with problems typically attributed to central or peripheral nerve involvement. Acknowledging vestibular dysfunction as part of the presentation provides an opportunity to access targeted vestibular rehabilitation, for which extensive evidence exists. A diagnostic framework was developed and validated to detect vestibular dysfunction, benign paroxysmal positional vertigo or vestibular migraine. The specificity and sensitivity of the diagnostic framework was tested in patients with primary mitochondrial disease. METHODS: Adults with a confirmed diagnosis of primary mitochondrial disease were consented, between September 2020 and February 2022. Participants with and without dizziness or unsteadiness underwent remote physiotherapy assessment and had in-person detailed neuro-otological assessment. The six framework question responses were compared against objective neuro-otological assessment or medical notes. The output was binary, with sensitivity and specificity calculated. RESULTS: Seventy-four adults completed the study: age range 20-81 years (mean 48 years, ±SD 15.05 years); ratio 2:1 female to male. The framework identified a vestibular diagnosis in 35 participants, with seven having two diagnoses. The framework was able to identify vestibular diagnoses in adults with primary mitochondrial disease, with a moderate (40-59) to very high (90-100) sensitivity and positive predictive value, and moderate to high (60-74) to very high (90-100) specificity and negative predictive value. CONCLUSIONS: Overall, the clinical framework identified common vestibular diagnoses with a moderate to very high specificity and sensitivity. This presents an opportunity for patients to access effective treatment in a timely manner, to reduce falls and improve quality of life.

Neurological gait assessment.

Gait disorders are a common feature of neurological disease. The gait examination is an essential part of the neurological clinical assessment, providing valuable clues to a myriad of causes. Understanding how to examine gait is not only essential for neurological diagnosis but also for treatment and prognosis. Here, we review aspects of the clinical history and examination of neurological gait to help guide gait disorder assessment. We focus particularly on how to differentiate between common gait abnormalities and highlight the characteristic features of the more prevalent neurological gait patterns such as ataxia, waddling, steppage, spastic gait, Parkinson's disease and functional gait disorders. We also offer diagnostic clues for some unusual gait presentations, such as dystonic, stiff-person and choreiform gait, along with red flags that help differentiate atypical parkinsonism from Parkinson's disease.

What's in a Name? Chronic Vestibular Migraine or Persistent Postural Perceptual Dizziness?

Current consensus diagnostic criteria for vestibular migraine (VM) describes this as an episodic disorder. However, a minority of patients report prolonged (>72 h duration) or even persistent VM symptoms, prompting whether a chronic variant of vestibular migraine (CVM) should be introduced to the current classification and how best to define it. Here we summarize current evidence of such a potential chronic variant of VM and critically review proposed definitions for CVM. Potential approaches to establish a diagnostic framework for CVM include (a) following the distinction between episodic and chronic migraine headaches, namely, frequent and/or prolonged episodes of VM (but not persistent vertigo or dizziness) in the context of chronic migraine headaches or (b) daily dizzy spells over more than 6 months that responded well to prophylactic anti-migraine therapy. A key challenge when defining diagnostic criteria for CVM is how to distinguish it from other chronic vestibular syndromes such as motion sickness, persistent postural-perceptual dizziness (PPPD), and mal de débarquement syndrome. Indeed, more than 50% of patients with PPPD and up to 46% with mal de débarquement syndrome fulfil diagnostic criteria for episodic migraine headaches, suggesting these disorders may all lie along a spectrum. We propose that when VM becomes persistent, it is best classified as PPPD but that VM and PPPD are not mutually exclusive, such that patients with PPPD need not have features of VM, and the triggering event for persistent dizziness may be independent of migraine. However, further research is needed to better characterize the spectrum of clinical phenotypes in patients with chronic dizziness, migraine headaches and anxiety, to define whether a chronic variant of VM sufficiently differs from current persistent dizziness definitions.

Acute positional vertigo in the emergency department-peripheral vs. central positional nystagmus.

Introduction: Benign paroxysmal positional vertigo (BPPV) is the most common cause of positional vertigo. However, positional vertigo can also be due to diseases affecting the central vestibular pathways, such as vestibular migraine. Accurate and timely diagnosis enables effective triage and management. Objectives: To evaluate diagnoses made by emergency clinicians compared to acute vertigo specialists, in patients presenting to an emergency department (ED) with positional vertigo. Methods: Following routine ED care, patients with a primary complaint of dizziness, vertigo, light-headedness or unsteadiness, underwent detailed neuro-otological assessment by acute vertigo specialists. Demographics and final diagnoses were recorded and analyzed. Results: Of 71 consented patients (21-91 years; mean 56 years, ±16.7 years, 40 females), ED identified 13 with a peripheral cause of positional vertigo (mean 48.85 years, ±16.19, 8 females). Central positional nystagmus was not noted in any of the patients with positional vertigo seen by the ED clinicians. Acute vertigo specialists diagnosed nine patients with BPPV (age range 50-88 years, mean 66 years, ±12.22, 5 females), and six with central positional nystagmus (age range 23-59 years, mean 41.67 years, ±15.78, 6 females). Conclusion: Positional vertigo should be assessed with positional maneuvers such as Dix-Hallpike and Roll tests in the ED to identify peripheral and central nystagmus features. Central causes are more common in younger females, with the presence of vomiting, and/or a background of motion sensitivity.

Neuroinflammatory disorders of the brain and inner ear: a systematic review of auditory function in patients with migraine, multiple sclerosis, and neurodegeneration to support the idea of an innovative 'window of discovery'.

Background: Hearing can be impaired in many neurological conditions and can even represent a forme fruste of specific disorders. Auditory function can be measured by either subjective or objective tests. Objective tests are more useful in identifying which auditory pathway (superior or inferior) is most affected by disease. The inner ear's perilymphatic fluid communicates with the cerebrospinal fluid (CSF) via the cochlear aqueduct representing a window from which pathological changes in the contents of the CSF due to brain inflammation could, therefore, spread to and cause inflammation in the inner ear, damaging inner hair cells and leading to hearing impairment identifiable on tests of auditory function. Methods: A systematic review of the literature was performed, searching for papers with case-control studies that analyzed the hearing and migraine function in patients with neuro-inflammatory, neurodegenerative disorders. With data extracted from these papers, the risk of patients with neurological distortion product otoacoustic emission (DPOAE) was then calculated. Results: Patients with neurological disorders (headache, Parkinson's disease, and multiple sclerosis) had a higher risk of having peripheral auditory deficits when compared to healthy individuals. Conclusion: Existing data lend credence to the hypothesis that inflammatory mediators transmitted via fluid exchange across this communication window, thereby represents a key pathobiological mechanism capable of culminating in hearing disturbances associated with neuroimmunological and neuroinflammatory disorders of the nervous system.

Vestibular loss disrupts visual reactivity in the alpha EEG rhythm.

The alpha rhythm is a dominant electroencephalographic oscillation relevant to sensory-motor and cognitive function. Alpha oscillations are reactive, being for example enhanced by eye closure, and suppressed following eye opening. The determinants of inter-individual variability in reactivity in the alpha rhythm (e.g. changes with amplitude following eye closure) are not fully understood despite the physiological and clinical applicability of this phenomenon, as indicated by the fact that ageing and neurodegeneration reduce reactivity. Strong interactions between visual and vestibular systems raise the theoretical possibility that the vestibular system plays a role in alpha reactivity. To test this hypothesis, we applied electroencephalography in sitting and standing postures in 15 participants with reduced vestibular function (bilateral vestibulopathy, median age = 70 years, interquartile range = 51-77 years) and 15 age-matched controls. We found participants with reduced vestibular function showed less enhancement of alpha electroencephalography power on eye closure in frontoparietal areas, compared to controls. In participants with reduced vestibular function, video head impulse test gain - as a measure of residual vestibulo-ocular reflex function - correlated with reactivity in alpha power across most of the head. Greater reliance on visual input for spatial orientation ('visual dependence', measured with the rod-and-disc test) correlated with less alpha enhancement on eye closure only in participants with reduced vestibular function, and this was partially moderated by video head impulse test gain. Our results demonstrate for the first time that vestibular function influences alpha reactivity. The results are partly explained by the lack of ascending peripheral vestibular input but also by central reorganisation of processing relevant to visuo-vestibular judgements.

The vestibular system: Contributions of Lorente de Nó.

BACKGROUND: Rafael Lorente de Nó was a neuroscientist that worked alongside two of the giants of Medicine, the Nobel Prize winners Cajal and Bárány. OBJECTIVE: To describe the contributions of Lorente de Nó to vestibular neuroscience. METHODS: Detailed review of the publications of Lorente de Nó and analysis of the archives from Junta para Ampliación de Estudios e Investigaciones Científicas at Residencia de Estudiantes (Madrid, Spain), Casa de Salud Valdecilla at Hospital Universitario Marqués de Valdecilla (Santander, Spain), Becker Medical Library at Washington University (St. Louis, MO, USA), Rockefeller Archive Center (Sleepy Hollow, New York, NY, USA), Archivo Fernando de Castro (Madrid, Spain), Biblioteca Nacional de España (Madrid, Spain) and Legado Cajal at Instituto Cajal (Madrid, Spain). Most of this material is unpublished and includes over a hundred letters to or from Lorente. RESULTS: Lorente de Nó made a substantial contribution to our understanding of the vestibular system. Amongst these, he meticulously detailed the course of the vestibular nerve and its central projections. He described the vestibulo-ocular reflex as the consequence of an integration of the various nuclei and connections across the vestibular system, rather than a simple three-neuron arc. He also highlighted the role of the reticular formation in the generation of the fast phase of the nystagmus. CONCLUSIONS: Lorente de Nó was a pioneer of modern neuro-otology, having made outstanding contributions to vestibular neuroscience, forging novel discoveries that still burn true today.