Risk of falls, vestibular multimodal processing, and multisensory integration decline in the elderly-Predictive role of the functional head impulse test

Age-related degeneration of the vestibular system, also known as presbyastasis, leads to unstable gait and higher risk of falls. These conditions affect lifestyle and may have non-negligible social repercussions due to fear-related states of anxiety and depression. In order to develop a model for predicting risk of falls, we assessed vestibulo-ocular function by video and functional Head Impulse Tests (vHIT and fHIT) and their possible correlations with Tinetti Balance Test score. Thirty-one patients over 65 years of age admitted with trauma due to falls were recruited. Vestibular evaluation (complete otoneurological assessment, vHIT, fHIT), cognitive tests (Mini Mental State Examination), anxiety and depression evaluation and Tinetti Balance Test were performed. The possibility of a correlation between the head impulse tests (vHIT, fHIT) and the Tinetti Balance Test was investigated by logistic regression analysis (Nagelkerke r(2) and Wald test). A linear correlation was found between the Tinetti Balance Test score and fHIT, whereas no correlation was found for vHIT. Functional HIT is an effective test for predicting the risk of falls in elderly patients

A Wearable Wireless Magnetic Eye-Tracker, in-vitro and in-vivo tests

A wireless, wearable magnetic eye tracker is described and characterized. The proposed instrumentation enables simultaneous evaluation of eye and head angular displacements. Such a system can be used to determine the absolute gaze direction as well as to analyze spontaneous eye re-orientation in response to stimuli consisting in head rotations. The latter feature has implications to analyze the vestibulo-ocular reflex and constitutes an interesting opportunity to develop medical (oto-neurological) diagnostics. Details of data analysis are reported together with some results obtained in-vivo or with simple mechanical simulators that enable measurements under controlled conditions

Frequency-dependent tuning of the human vestibular "sixth sense" by transcranial oscillatory currents

Objective: The vestibular cortex is a multisensory associative region that, in neuroimaging investigations, is activated by slow-frequency (1-2 Hz) galvanic stimulation of peripheral receptors. We aimed to directly activate the vestibular cortex with biophysically modeled transcranial oscillatory current stimulation (tACS) in the same frequency range. Methods: Thirty healthy subjects and one rare patient with chronic bilateral vestibular deafferentation underwent, in a randomized, double-blind, controlled trial, to tACS at slow (1 or 2 Hz) or higher (10 Hz) frequency and sham stimulations, over the Parieto-Insular Vestibular Cortex (PIVC), while standing on a stabilometric platform. Subjective symptoms of motion sickness were scored by Simulator Sickness Questionnaire and subjects' postural sways were monitored on the platform. Results: tACS at 1 and 2 Hz induced symptoms of motion sickness, oscillopsia and postural instability, that were supported by posturographic sway recordings. Both 10 Hz-tACS and sham stimulation on the vestibular cortex did not affect vestibular function. As these effects persisted in a rare patient with bilateral peripheral vestibular areflexia documented by the absence of the Vestibular-Ocular Reflex, the possibility of a current spread toward peripheral afferents is unlikely. Conversely, the 10 Hz-tACS significantly reduced his chronic vestibular symptoms in this patient. Conclusions: Weak electrical oscillations in a frequency range corresponding to the physiological cortical activity of the vestibular system may generate motion sickness and postural sways, both in healthy subjects and in the case of bilateral vestibular deafferentation. Significance: This should be taken into account as a new side effect of tACS in future studies addressing cognitive functions. Higher frequencies of stimulation applied to the vestibular cortex may represent a new interventional option to reduce motion sickness in different scenarios

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Alexander Crum Brown: A Forgotten Pioneer in Vestibular Sciences

Although vestibular anatomy was described in the Renaissance period, research in vestibular physiology began in the 1820s and was spearheaded by Purkinje and Flourens. This was subsequently expanded by Meniere, Helmholtz, Goltz, Mach, Breuer, Ewald, and Hogyes, who are regarded as the early pioneers in research on vestibular physiology in the 19th century. The relationship of endolymphatic flow and semicircular canal function is termed theMach-Breuer hypothesis. What is less well known is that a Scottish chemist, Alexander Crum Brown, arrived at similar conclusions as Mach and Breuer at the same time quite independently. In fact, he pioneered several concepts in vestibular physiology that included pairing of semicircular canals for function, the vestibular pathway, optic fixation elimination in vestibular experimentation, the theory of motion intolerance, and study in deaf mutes for insights into vestibular pathology and vestibular compensation. This article is a tribute to this forgotten pioneer in vestibular research

Acute Vestibular Neuritis: Prognosis Based upon Bedside Clinical Tests (Trusts and Heaves)

We compared bedside tests of vestibulo-ocular function (head thrust and head heave signs) with caloric testing results in 68 patients with acute vestibular neuritis seen at onset and in follow-up for one year. The head thrust and head heave signs each were strong predictors of a decreased probability of recovery, and if both were present, there was a trend for a slower recovery and a further decrease in the probability of recovery. If the head thrust sign was absent, recovery was assured. Our results suggest that careful bedside testing of semicircular canal (head thrust maneuver) and otolith (head heave maneuver) function provides useful information for predicting prognosis in patients with acute vestibular neuritis

Vincent Van Gogh and the elusive diagnosis of vestibular migraine

Vincent Van Gogh (1853-1890) was a creative genius and one of the greatest painters in history. He was a troubled soul plagued with an inner turmoil driven by his social, financial, personality and medical/psychiatric afflictions. His life has fascinated academic scholars of many disciplines who have researched extensively on his life and works. From his voluminous correspondences and contemporary medical records, his medical/psychiatric illnesses have been analysed in detail and several diagnostic formulations proposed. These include temporal lobe epilepsy, intermittent acute porphyria, Meniere's disease, lead poisoning, sexually transmitted diseases, terpene/absinthe/alcohol abuse, ophthalmological disorders in addition to chronic bipolar disorder, schizophrenia, personality and anxiety disorder and narcissism/neuroticism. We hypothesized a new diagnosis in the form of vestibular migraine for Van Gogh which is a migraine variant but distinct from the classical migraine variety. Our hypothesis is unique as it also considers that this condition due to its recognised associations with Van Gogh's proposed illnesses could have influenced his other conditions and thus offers a common unifying factor to explain his illness symptoms. We tested our hypothesis by individually analysing all of Van Gogh's correspondences in the original French and Dutch as well as English translations. Further, we considered the existing literature on Van Gogh's other illnesses and contemporary medical records. Van Gogh fulfilled all the criteria for vestibular migraine as formulated by Barany Society and International Classification of Headache Disorders (ICHD) 3 with episodic dizziness, present or past history of classical migraine, headache, photophobia, phonophobia and visual and position triggered vertigo with no other otologial cause to explain his symptoms (including Meniere's disease). Furthermore, it appears that vestibular migraine could have interacted with most of his other proposed illnesses. We also observed that this condition influenced his art following onset for example, in his use of colours and depiction of his subject matter with a consistent vertical tilt on the left. It is anticipated that our hypothesis will add a new dimension to the understanding of his illnesses and increase the awareness of the complex condition of vestibular migraine that to this day has limited awareness amongst the medical and general fraternity

Caloric stimulation of the labyrinth and some forgotten pioneers

Introduction: Understanding the physiology of the caloric stimulation of the vestibular end organ was a seminal discovery in the history of neurotology. Robert Barany has been traditionally credited with this (1906). However, well before Barany, three scientists observed, qualified and quantified a similar phenomenon with different explanations. They were Charles Edouard Brown Sequard (1858), A Bornhardt (1876) and Benno Baginsky (1881)