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 human vestibular cortex: functional anatomy of OP2, its connectivity and the effect of vestibular disease.

Area OP2 in the posterior peri-sylvian cortex has been proposed to be the core human vestibular cortex. We investigated the functional anatomy of OP2 and adjacent areas (OP2+) using spatially constrained independent component analysis (ICA) of functional magnetic resonance imaging (fMRI) data from the Human Connectome Project. Ten ICA-derived subregions were identified. OP2+ responses to vestibular and visual motion were analyzed in 17 controls and 17 right-sided vestibular neuritis patients who had previously undergone caloric and optokinetic stimulation during fMRI. In controls, a posterior part of right OP2+ showed: (i) direction-selective responses to visual motion and (ii) activation during caloric stimulation that correlated positively with perceived self-motion, and negatively with visual dependence and peak slow-phase nystagmus velocity. Patients showed abnormal OP2+ activity, with an absence of visual or caloric activation of the healthy ear and no correlations with vertigo or visual dependence-despite normal slow-phase nystagmus responses to caloric stimulation. Activity in a lateral part of right OP2+ correlated with chronic visually induced dizziness in patients. In summary, distinct functional subregions of right OP2+ show strong connectivity to other vestibular areas and a profile of caloric and visual responses, suggesting a central role for vestibular function in health and disease.

A link between frontal white matter integrity and dizziness in cerebral small vessel disease.

One in three older people (>60 years) complain of dizziness which often remains unexplained despite specialist assessment. We investigated if dizziness was associated with vascular injury to white matter tracts relevant to balance or vestibular self-motion perception in sporadic cerebral small vessel disease (age-related microangiopathy). We prospectively recruited 38 vestibular clinic patients with idiopathic (unexplained) dizziness and 36 age-matched asymptomatic controls who underwent clinical, cognitive, balance, gait and vestibular assessments, and structural and diffusion brain MRI. Patients had more vascular risk factors, worse balance, worse executive cognitive function, and worse ankle vibration thresholds in association with greater white matter hyperintensity in frontal deep white matter, and lower fractional anisotropy in the genu of the corpus callosum and the right inferior longitudinal fasciculus. A large bihemispheric white matter network had less structural connectivity in patients. Reflex and perceptual vestibular function was similar in patients and controls. Our results suggest cerebral small vessel disease is involved in the genesis of dizziness through its effect on balance.

Electroencephalographic response to transient adaptation of vestibular perception.

When given a series of sinusoidal oscillations in which the two hemicycles have equal amplitude but asymmetric velocity, healthy subjects lose perception of the slower hemicycle (SHC), reporting a drift towards the faster hemicycle (FHC). This response is not reflected in the vestibular-ocular reflex, suggesting that the adaptation is of higher order. This study aimed to define EEG correlates of this adaptive response. Twenty-five subjects underwent a series of symmetric or asymmetric oscillations and reported their perceived head orientation at the end using landmarks in the testing room; this was converted into total position error (TPE). Thirty-two channel EEG was recorded before, during and after adaptation. Spectral power and coherence were calculated for the alpha, beta, delta and theta frequency bands. Linear mixed models were used to determine a region-by-condition effect of the adaptation. TPE was significantly greater in the asymmetric condition and reported error was always in the direction of the FHC. Regardless of condition, alpha desynchronised in response to stimulation, then rebounded back toward baseline values. This pattern was accelerated and attenuated in the prefrontal and occipital regions, respectively, in the asymmetric condition. Functional connectivity networks were identified in the beta and delta frequency bands; these networks, primarily comprising frontoparietal connections, were more coherent during asymmetric stimulation. These findings suggest that the temporary vestibulo-perceptual 'neglect' induced by asymmetric vestibular stimulation may be mediated by alpha rhythms and frontoparietal attentional networks. The results presented further our understanding of brain rhythms and cortical networks involved in vestibular perception and adaptation. KEY POINTS: Whole-body asymmetric sinusoidal oscillations, which consist of hemicycles with equal amplitude but differing velocities, can induce transient 'neglect' of the slower hemicycle in the vestibular perception of healthy subjects. In this study, we aimed to elucidate EEG correlates of this 'neglect', thereby identifying a cortical role in vestibular perception and adaptation. We identified a desynchronisation-resynchronisation response in the alpha frequency band (8-14 Hz) that was accelerated in the prefrontal region and attenuated in the occipital region when exposed to asymmetric, as compared to symmetric, rotations. We additionally identified functional connectivity networks in the beta (14-30 Hz) and delta (1-4 Hz) frequency bands consisting primarily of frontoparietal connections. These results suggest a prominent role of alpha rhythms and frontoparietal attentional networks in vestibular perception and adaptation.

Endovascular treatment for vaccine-induced cerebral venous sinus thrombosis and thrombocytopenia following ChAdOx1 nCoV-19 vaccination: a report of three cases.

BACKGROUND: Vaccine-induced thrombosis and thrombocytopenia (VITT) is a rare complication following ChAdOx1 nCoV-19 vaccination. Cerebral venous sinus thrombosis (CVST) is overrepresented in VITT and is often associated with multifocal venous thromboses, concomitant hemorrhage and poor outcomes. Hitherto, endovascular treatments have not been reviewed in VITT-related CVST. METHODS: Patient records from a tertiary neurosciences center were reviewed to identify patients who had endovascular treatment for CVST in VITT. RESULTS: Patient records from 1 January 2021 to 20 July 2021 identified three patients who underwent endovascular treatment for CVST in the context of VITT. All were female and the median age was 52 years. The location of the CVST was highly variable. Two-thirds of the patients had multifocal dural sinus thromboses (sigmoid, transverse, straight and superior sagittal) as well as internal jugular vein thromboses. Intracerebral hemorrhage occurred in all patients; subarachnoid blood was noted in two of them, and intraparenchymal hemorrhage occurred in all. There was one periprocedural parenchymal extravasation which abated on temporary cessation of anticoagulation. Outcome data revealed a 90-day modified Rankin Scale (mRS) score of 2 in all cases. CONCLUSIONS: We demonstrate that endovascular treatment for VITT-associated CVST is feasible and can be safe in cases that deteriorate despite medical therapy. Extensive clot burden, concomitant hemorrhage, rapid clinical progression and persistent rises in intracranial pressure should initiate multidisciplinary team discussion for endovascular treatment in appropriate cases.

Consensus on Virtual Management of Vestibular Disorders: Urgent Versus Expedited Care.

The virtual practice has made major advances in the way that we care for patients in the modern era. The culture of virtual practice, consulting, and telemedicine, which had started several years ago, took an accelerated leap as humankind was challenged by the novel coronavirus pandemic (COVID19). The social distancing measures and lockdowns imposed in many countries left medical care providers with limited options in evaluating ambulatory patients, pushing the rapid transition to assessments via virtual platforms. In this novel arena of medical practice, which may form new norms beyond the current pandemic crisis, we found it critical to define guidelines on the recommended practice in neurotology, including remote methods in examining the vestibular and eye movement function. The proposed remote examination methods aim to reliably diagnose acute and subacute diseases of the inner-ear, brainstem, and the cerebellum. A key aim was to triage patients into those requiring urgent emergency room assessment versus non-urgent but expedited outpatient management. Physicians who had expertise in managing patients with vestibular disorders were invited to participate in the taskforce. The focus was on two topics: (1) an adequate eye movement and vestibular examination strategy using virtual platforms and (2) a decision pathway providing guidance about which patient should seek urgent medical care and which patient should have non-urgent but expedited outpatient management.

Theoretical framework for "unexplained" dizziness in the elderly: The role of small vessel disease.

In this paper we postulate that disruption of connectivity in the human brain can lead to dizziness, a symptom normally associated with focal disease of the vestibular system. The specific case that we will examine is the development of "unexplained" dizziness in the elderly-an extremely common clinical problem. Magnetic resonance imaging of the brain in the elderly usually show variable degrees of multifocal micro-angiopathy (small vessel white matter disease, SVD); thus, we review the literature, present a conceptual model and report preliminary quantitative EEG data in support of the hypothesis that such hemispheric SVD leads to central nervous system disconnection that elderly patients report as dizziness. Loss of connectivity by age-related build-up of SVD could lead to dizzy feelings through one or more of the following mechanisms: disconnection of cortical vestibular centers, disconnection between frontal gait centers and the basal ganglia, and disconnection between intended motor action (efference copy) and sensory re-afference. Finally, we propose that SVD-mediated dysregulation of cerebral blood pressure is linked to dizziness during standing and walking in elderly patients with "unexplained" dizziness.

Neurosarcoidosis: a clinical approach to diagnosis and management.

Sarcoidosis is a rare but important cause of neurological morbidity, and neurological symptoms often herald the diagnosis. Our understanding of neurosarcoidosis has evolved from early descriptions of a uveoparotid fever to include presentations involving every part of the neural axis. The diagnosis should be suspected in patients with sarcoidosis who develop new neurological symptoms, those presenting with syndromes highly suggestive of neurosarcoidosis, or neuro-inflammatory disease where more common causes have been excluded. Investigation should look for evidence of neuro-inflammation, best achieved by contrast-enhanced brain magnetic resonance imaging and cerebrospinal fluid analysis. Evidence of sarcoidosis outside the nervous system should be sought in search of tissue for biopsy. Skin lesions should be identified and biopsies taken. Chest radiography including high-resolution computed tomography is often informative. In difficult cases, fluorodeoxyglucose positron emission tomography and gallium-67 imaging may identify subclinical disease and a target for biopsy. Symptomatic patients should be treated with corticosteroids, and if clinically indicated other immunosuppressants such as hydroxychloroquine, azathioprine, cyclophosphamide or methotrexate should be added. Anti-tumour necrosis factor alpha therapies may be considered in refractory disease but caution should be exercised as there is evidence to suggest they may unmask disease.

Oxidative stress-related biomarkers in multiple sclerosis: a review.

AIM: To provide an up-to-date review of oxidative stress biomarkers in multiple sclerosis and thus identify candidate molecules with greatest promise as biomarkers of diagnosis, disease activity or prognosis. METHOD: A semi-systematic literature search using PubMed and other databases. RESULTS: Nitric oxide metabolites, superoxide dismutase, catalase, glutathione reductase, inducible nitric oxide synthase, protein carbonyl, 3-nitrotyrosine, isoprostanes, malondialdehyde and products of DNA oxidation have been identified across multiple studies as having promise as diagnostic, therapeutic or prognostic markers in MS. CONCLUSION: Heterogeneity of study design, particularly patient selection, limits comparability across studies. Further cohort studies are needed, and we would recommend promising markers be incorporated into future clinical trials to prospectively validate their potential.

Getting the basics right: delays in phlebotomy and intravenous cannulation: a survey of foundation year 1 doctors.

Junior doctors frequently experience delays in routine ward-based procedures. There is little published data on this subject, but it is clear that such delays can have implications in terms of costs, efficiency, length of patient stay, team working and patient safety and experience. We formulated an anonymous online survey to quantify the experiences of foundation year 1 (FY1) doctors with respect to phlebotomy services and intravenous (IV) cannulation. We gathered data on equipment availability, time taken to carry out these tasks and the factors thought to contribute to delays. The results were compared to clinically relevant standards. Between April and August 2012, 199 responses were received. For IV cannulation, 21% of doctors reported equipment availability as 'very good', but only 3% said that they were able to find all of the pieces of equipment they needed close to each other ('essentially in the same place'). Similar results were obtained for phlebotomy. Nevertheless, there appears to be significant room for improvement and we offer recommendations to address delays.

Pitfalls in the management of herpes simplex virus encephalitis.

We report a case of Herpes Simplex Virus Encephalitis (HSVE) with a fatal outcome of a patient in his 70s presenting to a local teaching hospital with fever and confusion. We highlight pertinent issues regarding diagnosis, investigation and management, and consider ways of improving clinical outcomes. Finally, we discuss the differential diagnoses of acute encephalitis and review the management of HSVE.

Churg-Strauss syndrome in a patient previously diagnosed with multiple sclerosis.

A lady in her 70s with a background of multiple sclerosis (MS) and late-onset asthma was admitted with a 2-week history of cough and shortness of breath, progressive right-sided weakness and functional decline. Investigation revealed eosinophilia, elevated myeloperoxidase antineutrophil cytoplasmic antibody, CT sinuses showed long-standing inflammatory changes consistent with sinonasal polyposis and MRI head showed lesions consistent with vasculitis. She then developed left-sided weakness and increased wheeze. Review of her case notes demonstrated that, the eosinophilia was long-standing, her asthma was severe and steroid-dependent, and her neurologic syndrome was atypical for MS. Intravenous methylprednisolone then cyclophosphamide were administered. She demonstrated remarkable improvement, becoming more alert, with improvement in left-sided weakness. A diagnosis of Churg-Strauss syndrome was established. She was discharged to a nursing home with outpatient rheumatology follow-up. The diagnosis of MS was revisited.