Machine learning models help differentiate between causes of recurrent spontaneous vertigo.

BACKGROUND: Vestibular migraine (VM) and Menière's disease (MD) are two common causes of recurrent spontaneous vertigo. Using history, video-nystagmography and audiovestibular tests, we developed machine learning models to separate these two disorders. METHODS: We recruited patients with VM or MD from a neurology outpatient facility. One hundred features from six "feature subsets": history, acute video-nystagmography and four laboratory tests (video head impulse test, vestibular-evoked myogenic potentials, caloric testing and audiogram) were used. We applied ten machine learning algorithms to develop classification models. Modelling was performed using three "tiers" of data availability to simulate three clinical settings. "Tier 1" used all available data to simulate the neuro-otology clinic, "Tier 2" used only history, audiogram and caloric test data, representing the general neurology clinic, and "Tier 3" used history alone as occurs in primary care. Model performance was evaluated using tenfold cross-validation. RESULTS: Data from 160 patients with VM and 114 with MD were used for model development. All models effectively separated the two disorders for all three tiers, with accuracies of 85.77-97.81%. The best performing algorithms (AdaBoost and Random Forest) yielded accuracies of 97.81% (95% CI 95.24-99.60), 94.53% (91.09-99.52%) and 92.34% (92.28-96.76%) for tiers 1, 2 and 3. The best feature subset combination was history, acute video-nystagmography, video head impulse test and caloric testing, and the best single feature subset was history. CONCLUSIONS: Machine learning models can accurately differentiate between VM and MD and are promising tools to assist diagnosis by medical practitioners with diverse levels of expertise and resources.

Modern vestibular tests can accurately separate stroke and vestibular neuritis.

OBJECTIVES: To separate posterior-circulation stroke (PCS) and vestibular-neuritis (VN) using quantitative vestibular tests. METHODS: Patients were prospectively recruited from the emergency room within 72 h of presentation. Video-nystagmography (VNG), three-dimensional video head-impulse testing (vHIT), vestibular-evoked myogenic potentials (VEMPs), and subjective visual-horizontal (SVH) were performed. RESULTS: There were 128 PCS and 134 VN patients. Common stroke-territories were: posterior-inferior cerebellar artery, basilar-perforators, multi-territory and anterior-inferior cerebellar artery (41.4%, 21.1%, 14.1%, 7.8%). VN included superior, inferior and pan-neuritis (53.3%, 4.2%, and 41.5%). Most VN and stroke patients presented with acute vestibular syndrome (96.6%, 61.7%). In VN, we recorded horizontal (98.5%) or vertical/torsional spontaneous nystagmus (1.5%) and in PCS, absent-nystagmus (53.9%), horizontal (32%) or vertical/torsional (14.1%) nystagmus. The mean slow-phase velocity of horizontal nystagmus was faster in VN than PCS (11.8 ± 7.2 and 5.2 ± 3.0°/s, p < 0.01). Ipsilesional horizontal-canal (HC) vHIT-gain was lower in VN than in stroke (0.47 ± 0.24, 0.92 ± 0.20, p < 0.001). Ipsilesional catch-up saccades occurred earlier, and their amplitude, prevalence, and velocity were greater in VN than PCS (p < 0.01). Ipsilesional SVH deviation > 2.5° occurred more often in VN than in stroke (97.6% and 24.3%, p < 0.01). Abnormal bone-conducted ocular-VEMP asymmetry ratio was more common in VN than PCS (50% and 14.4%, p < 0.01). Using the ten best discriminators (VNG, vHIT, SVH, and oVEMP metrics), VN was separated from PCS with a sensitivity of 92.9% and specificity of 89.8%. Adding VNG and vHIT to the bedside head-impulse-nystagmus-and-test-of-skew (HINTS) test enhanced sensitivity and specificity from 95.3% and 63.4% to 96.5% and 80.6%. CONCLUSION: Quantitative vestibular testing helps separate stroke from vestibular neuritis and, when used, could improve diagnostic accuracy in the emergency room.

The human vestibulo-ocular reflex and compensatory saccades in schwannoma patients before and after vestibular nerve section.

OBJECTIVE: To examine the vestibulo-ocular reflex (VOR) and compensatory-saccades before and after complete unilateral vestibular deafferentation (UVD). METHODS: Forty patients were studied before and after surgery for vestibular or facial schwannoma using the video head-impulse test (vHIT) and multivariable regression. RESULTS: Prior to UVD (median(IQR), 14(58.4) days), the average VOR-gain towards the lesioned-ear was lower than in normal for all semicircular canals (lateral, anterior, posterior: 0.69, 0.72, 0.49). One-week after UVD (5(3.0) days) VOR gains were further reduced (0.22, 0.37, 0.27), however, within one-year after UVD (171(125.0) days) the lesioned-ear VOR gains had slightly increased (+0.08, +0.11, +0.03), maximally for the anterior-canal. After UVD, the VOR gain asymmetry (gain towards minus away from intact-ear) was lower for the intact posterior-canal plane (0.56, 0.56, 0.22). For the lesioned canals, the frequency and amplitude of the first compensatory-saccade increased from 61-93% and 1.9-3.6° pre-surgery, to 98-99% and to 3.1-5.9° one-week post-surgery and remained unchanged over one-year; second saccade frequency and amplitude decreased over the same timespan. CONCLUSIONS: After UVD the high-acceleration VOR for the intact posterior-canal plane is more symmetrical than the other canals. First compensatory-saccades adapt within one week and subsequently change only marginally. SIGNIFICANCE: Saccade compensation from surgical UVD is near complete by one-week.

A Portrait of Menière's Disease Using Contemporary Hearing and Balance Tests.

OBJECTIVE: Menière's disease (MD) is characterized by recurrent vertigo and fluctuating aural symptoms. Diagnosis is straightforward in typical presentations, but a proportion of patients present with atypical symptoms. Our aim is to profile the array of symptoms patients may initially present with and to analyze the vestibular and audiological test results of patients with a diagnosis of MD. DESIGN: A retrospective study of patient files. SETTING: A tertiary, neuro-otology clinic Royal Prince Alfred Hospital, Sydney, Australia. METHOD: We identified 375 patients. Their history, examination, vestibular-evoked myogenic potentials (VEMP), video head-impulse test, canal-paresis on caloric testing, subjective visual horizontal (SVH), electrocochleography, ictal nystagmus, and audiometry were assessed. RESULTS: Atypical presenting symptoms were disequilibrium (n = 49), imbalance (n = 13), drop-attacks (n = 12), rocking vertigo (n = 2), and unexplained vomiting (n = 3), nonspontaneous vestibular symptoms in 21.6%, fluctuation of aural symptoms only (46%), and headaches (31.2%). Low velocity, interictal spontaneous-nystagmus in 13.3% and persistent positional-nystagmus in 12.5%. Nystagmus recorded ictally in 90 patients was mostly horizontal (93%) and of high velocity (48 ±â€Š34°/s). Testing yielded abnormal caloric responses in 69.6% and abnormal video head impulse test 12.7%. Air-conducted cervical VEMPs were abnormal in 32.2% (mean asymmetry ratio [AR] 30.2 ±â€Š46.5%) and bone-conducted ocular VEMPs abnormal in 8.8% (AR 11.2 ±â€Š26.8%). Abnormal interictal SVH was in 30.6%, (ipsiversive n = 46 and contraversive n = 19). Mean pure-tone averages 50 dB ±â€Š23.5 and 20 dB ±â€Š13 for affected and unaffected ears. CONCLUSION: Menière's disease has a distinctive history, but atypical presentations with normal vestibular function and hearing are a diagnostic challenge delaying treatment initiation.

Capturing vertigo in the emergency room: three tools to double the rate of diagnosis.

OBJECTIVE: Many patients attending the emergency room (ER) with vertigo, leave without a diagnosis. We assessed whether the three tools could improve ER diagnosis of vertigo. METHODS: A prospective observational study was undertaken on 539 patients presenting to ER with vertigo. We used three tools: a structured-history and examination, nystagmus video-oculography (VOG) in all patients, additional video head-impulse testing (vHIT) for acute-vestibular-syndrome (AVS). RESULTS: In the intervention-group (n = 424), case-history classified AVS in 34.9%, episodic spontaneous-vertigo (ESV 32.1%), and episodic positional-vertigo (EPV 22.6%). In AVS, we employed "Quantitative-HINTS plus" (Head-Impulse, Nystagmus and Test-of-Skew quantified by vHIT and VOG, audiometry) to identify vestibular-neuritis (VN) and stroke (41.2 and 31.1%). vHIT gain ≤ 0.72, catch-up saccade amplitude > 1.4○, saccade-frequency > 154%, and unidirectional horizontal-nystagmus, separated stroke from VN with 93.1% sensitivity and 88.5% specificity. In ESV, 66.2 and 14% were diagnosed with vestibular migraine and Meniere's Disease by using history and audiometry. Horizontal-nystagmus velocity was lower in migraine 0.4 ± 1.6○/s than Meniere's 5.7 ± 5.5○/s (p < 0.01). In EPV, benign positional vertigo (BPV) was identified in 82.3% using VOG. Paroxysmal positional-nystagmus lasting < 60 s separated BPV from non-BPV with 90% sensitivity and 100% specificity. In the control group of ER patients undergoing management-as-usual (n = 115), diagnoses included BPV (38.3%) and non-specific vertigo (41.7%). Unblinded assessors reached a final diagnosis in 90.6 and 30.4% of the intervention and control groups. Blinded assessors provided with the data gathered from each group reached a diagnosis in 86.3 and 41.1%. CONCLUSION: Three tools: a structured-assessment, vHIT and VOG doubled the rate of diagnosis in the ER.

Clinical, oculographic and vestibular test characteristics of Ménière's disease.

Seventy Ménière's disease (MD) patients with spontaneous vertigo (100%), unilateral aural fullness (57.1%), tinnitus (78.6%), and subjective hearing loss (75.7%) self-recorded nystagmus during their episodes of vertigo using portable video oculography goggles. All demonstrated ictal spontaneous nystagmus, horizontal in 94.3% (n = 66) and vertical in 5.7% (n = 4), with a mean slow-phase velocity (SPV) of 42.8 ± 31.1°/s (range 5.3-160.1). Direction reversal of spontaneous horizontal nystagmus was captured in 58.6%, within the same episode in 34.3%, and over different days in 24.3%. In 18.6%, we observed ipsiversive then contraversive nystagmus, and in 12.9% contraversive to ipsiversive direction reversal. Ictal nystagmus SPV (42.8 ± 31.1°/s) was significantly faster than interictal (1.4 ± 3.1°/s, p < 0.001, CI 34.277-48.776). Compared to age-matched healthy controls, interictal video head impulse test gains in MD ears were significantly lower, cumulative and first saccade (S1) amplitudes were significantly larger, and S1 peak velocities were significantly faster (p = 0.038/0.019/0.008/ < 0.001, CI 0.002-0.071/0.130-1.444/0.138-0.909/14.614-41.506). Audiometry showed asymmetrically increased thresholds in 100% of MD ears (n = 70). Significant caloric, air-conducted (AC) cervical vestibular-evoked myogenic potential (VEMP), and AC ocular VEMP asymmetries were found in 61.4, 37.9, and 44.4% of patients (MD ear reduced). Transtympanic electrocochleography tested in 36 ears (23 patients) showed 81.8% of MD ears had a positive result for hydrops (either a summating potential at 1/2 kHz < - 6 µV, or an SP/AP ratio > 40%). Using ictal nystagmus findings of SPV > 12°/s, and a caloric canal paresis > 25%, we correctly separated a diagnosis MD from Vestibular Migraine with a sensitivity and specificity of 95.7% and 85.1% (CI 0.89-0.97).

Clinical, oculographic, and vestibular test characteristics of vestibular migraine.

BACKGROUND: We characterise the history, vestibular tests, ictal and interictal nystagmus in vestibular migraine. METHOD: We present our observations on 101 adult-patients presenting to an outpatient facility with recurrent spontaneous and/or positional vertigo whose final diagnosis was vestibular migraine (n = 27) or probable vestibular migraine (n = 74). Ictal and interictal video-oculography, caloric and video head impulse tests, vestibular-evoked myogenic potentials and audiometry were performed. RESULTS: Common presenting symptoms were headache (81.2%), spinning vertigo (72.3%), Mal de Débarquement (58.4%), and motion sensitivity (30.7%). With fixation denied, ictal and interictal spontaneous nystagmus was observed in 71.3 and 14.9%, and purely positional nystagmus in 25.8 and 55.4%. Spontaneous ictal nystagmus was horizontal in 49.5%, and vertical in 21.8%. Ictal spontaneous and positional nystagmus velocities were 5.3 ± 9.0°/s (range 0.0-57.4), and 10.4 ± 5.8°/s (0.0-99.9). Interictal spontaneous and positional nystagmus velocities were <3°/s in 91.8 and 23.3%. Nystagmus velocities were significantly higher when ictal (p < 0.001/confidence interval: 2.908‒6.733, p < 0.001/confidence interval: 5.308‒10.085). Normal lateral video head impulse test gains were found in 97.8% (mean gain 0.95 ± 0.12) and symmetric caloric results in 84.2% (mean canal paresis 7.0 ± 23.3%). Air- and bone-conducted cervical-vestibular-evoked myogenic potential amplitudes were symmetric in 88.4 and 93.4% (mean corrected amplitude 1.6 ± 0.7, 1.6 ± 0.8) with mean asymmetry ratios of 13.0 and 9.0%. Air- and bone-conducted ocular-vestibular-evoked myogenic potentials were symmetric in 67.7 and 97.2% (mean amplitude 9.2 ± 6.4 and 20.3 ± 12.8 µV) with mean asymmetry ratios of 15.7 and 9.9%. Audiometry was age consistent and symmetric in 85.5%. CONCLUSION: Vestibular migraine is characterised by low velocity ictal spontaneous nystagmus, which can be horizontal, vertical, or torsional, and normal audiovestibular test results.

Nystagmus characteristics of healthy controls.

BACKGROUND: Healthy controls exhibit spontaneous and positional nystagmus which needs to be distinguished from pathological nystagmus. OBJECTIVE: Define nystagmus characteristics of healthy controls using portable video-oculography. METHODS: One-hundred and one asymptomatic community-dwelling adults were prospectively recruited. Participants answered questions regarding their audio-vestibular and headache history and were sub-categorized into migraine/non-migraine groups. Portable video-oculography was conducted in the upright, supine, left- and right-lateral positions, using miniature take-home video glasses. RESULTS: Upright position spontaneous nystagmus was found in 30.7% of subjects (slow-phase velocity (SPV)), mean 1.1±2.2 degrees per second (°/s) (range 0.0 - 9.3). Upright position spontaneous nystagmus was horizontal, up-beating or down-beating in 16.7, 7.9 and 5.9% of subjects. Nystagmus in at least one lying position was found in 70.3% of subjects with 56.4% showing nystagmus while supine, and 63.4% in at least one lateral position. While supine, 20.8% of subjects showed up-beating nystagmus, 8.9% showed down-beating, and 26.7% had horizontal nystagmus. In the lateral positions combined, 37.1% displayed horizontal nystagmus on at least one side, while 6.4% showed up-beating, 6.4% showed down-beating. Mean nystagmus SPVs in the supine, right and left lateral positions were 2.2±2.8, 2.7±3.4, and 2.1±3.2°/s. No significant difference was found between migraine and non-migraine groups for nystagmus SPVs, prevalence, vertical vs horizontal fast-phase, or low- vs high-velocity nystagmus (<5 vs > 5°/s). CONCLUSIONS: Healthy controls without a history of spontaneous vertigo show low velocity spontaneous and positional nystagmus, highlighting the importance of interictal nystagmus measures when assessing the acutely symptomatic patient.

Separating posterior-circulation stroke from vestibular neuritis with quantitative vestibular testing.

OBJECTIVE: To separate vestibular neuritis (VN) from posteriorcirculation stroke (PCS) using quantitative tests of canal and otolith function. METHODS: Video Head-Impulse tests (vHIT) were used to assess all three semicircular canal pairs; vestibulo-ocular reflex (VOR) gain and saccade metrics were examined. Cervical and ocular-Vestibular-Evoked Myogenic Potentials (c- and oVEMP) and Subjective Visual Horizontal (SVH) were used to assess otolith function. RESULTS: For controls (n = 40), PCS (n = 22), and VN (n = 22), mean horizontal-canal VOR-gains were 0.96 ± 0.1, 0.85 ± 0.3 and 0.40 ± 0.2, refixation-saccade prevalence was 71.9 ± 41, 90.7 ± 57, 209.2 ± 62 per 100 impulses and cumulative-saccade amplitudes were 0.9 ± 0.4°, 2.4 ± 2.2°, 8.0 ± 3.5°. Abnormality-rates for cVEMP, oVEMP and SVH were 38%, 9%, 72% for PCS, and 43%, 50%, 91% for VN. A gain ≤0.68, refixation-saccade prevalence of ≥135% and cumulative-saccade amplitudes ≥5.3° separated VN from PCS with sensitivities of 95.5%, 95.5%, and 81.8%, and specificities of 68.2%, 86.4% and 95.5%. VOR-gain and saccade prevalence when combined, separated VN from PCS with a sensitivity and specificity of 90.9%. Abnormal oVEMP asymmetry-ratios were of low sensitivity (50%) but high specificity (90.9%) for separating VN from PCS. CONCLUSION: vHIT provided the best separation of VN from PCS. VOR-gain, refixation-saccade prevalence and amplitude were effective discriminators of VN from PCS. SIGNIFICANCE: vHIT and oVEMP could assist early identification of the aetiology of Acute Vestibular Syndrome in the Emergency Room.

Mesenchymal Stem Cell/Multipotent Stromal Cell Augmentation of Wound Healing: Lessons from the Physiology of Matrix and Hypoxia Support.

Cutaneous wounds requiring tissue replacement are often challenging to treat and result in substantial economic burden. Many of the challenges inherent to therapy-mediated healing are due to comorbidities of disease and aging that render many wounds as chronic or nonhealing. Repeated failure to resolve chronic wounds compromises the reserve or functioning of localized reparative cells. Transplantation of mesenchymal stem cells/multipotent stromal cells (MSCs) has been proposed to augment the reparative capacity of resident cells within the wound bed to overcome stalled wound healing. However, MSCs face a variety of challenges within the wound micro-environment that curtail their survival after transplantation. MSCs are naturally pro-angiogenic and proreparative, and thus numerous techniques have been attempted to improve their survival and efficacy after transplantation, many with little impact. These setbacks have prompted researchers to re-examine the normal wound bed physiology, resulting in new approaches to MSC transplantation using extracellular matrix proteins and hypoxia preconditioning. These studies have also led to new insights on associated intracellular mechanisms, particularly autophagy, which play key roles in further regulating MSC survival and paracrine signaling. This review provides a brief overview of cutaneous wound healing with discussion on how extracellular matrix proteins and hypoxia can be utilized to improve MSC retention and therapeutic outcome.

Head impulse compensatory saccades: Visual dependence is most evident in bilateral vestibular loss.

The normal vestibulo-ocular reflex (VOR) generates almost perfectly compensatory smooth eye movements during a 'head-impulse' rotation. An imperfect VOR gain provokes additional compensatory saccades to re-acquire an earth-fixed target. In the present study, we investigated vestibular and visual contributions on saccade production. Eye position and velocity during horizontal and vertical canal-plane head-impulses were recorded in the light and dark from 16 controls, 22 subjects after complete surgical unilateral vestibular deafferentation (UVD), eight subjects with idiopathic bilateral vestibular loss (BVL), and one subject after complete bilateral vestibular deafferentation (BVD). When impulses were delivered in the horizontal-canal plane, in complete darkness compared with light, first saccade frequency mean(SEM) reduced from 96.6(1.3)-62.3(8.9) % in BVL but only 98.3(0.6)-92.0(2.3) % in UVD; saccade amplitudes reduced from 7.0(0.5)-3.6(0.4) ° in BVL but were unchanged 6.2(0.3)-5.5(0.6) ° in UVD. In the dark, saccade latencies were prolonged in lesioned ears, from 168(8.4)-240(24.5) ms in BVL and 177(5.2)-196(5.7) ms in UVD; saccades became less clustered. In BVD, saccades were not completely abolished in the dark, but their amplitudes decreased from 7.3-3.0 ° and latencies became more variable. For unlesioned ears (controls and unlesioned ears of UVD), saccade frequency also reduced in the dark, but their small amplitudes slightly increased, while latency and clustering remained unchanged. First and second saccade frequencies were 75.3(4.5) % and 20.3(4.1) %; without visual fixation they dropped to 32.2(5.0) % and 3.8(1.2) %. The VOR gain was affected by vision only in unlesioned ears of UVD; gains for the horizontal-plane rose slightly, and the vertical-planes reduced slightly. All head-impulse compensatory saccades have a visual contribution, the magnitude of which depends on the symmetry of vestibular-function and saccade latency: BVL is more profoundly affected by vision than UVD, and second saccades more than first saccades. Saccades after UVD are probably triggered by contralateral vestibular function.

Dizziness demystified.

Four vestibular presentations caused by six different disorders constitute most of the neuro-otology cases seen in clinical practice. 'Acute vestibular syndrome' refers to a first-ever attack of acute, spontaneous, isolated vertigo and there are two common causes: vestibular neuritis / labyrinthitis and cerebellar infarction. Recurrent positional vertigo is most often caused by benign paroxysmal positional vertigo and less commonly is central in origin. Recurrent spontaneous vertigo has two common causes: Ménière's disease and vestibular migraine. Lastly, chronic vestibular insufficiency (imbalance) results from bilateral, or severe unilateral, peripheral vestibular impairment. These six disorders can often be diagnosed on the basis of history, examination, audiometry, and in some cases, basic vestibular function testing. Here we show that most common neuro-otological problems can be readily managed by general neurologists.

Capturing acute vertigo: A vestibular event monitor.

OBJECTIVE: To facilitate the diagnosis of vestibular disorders by patient-initiated capture of ictal nystagmus. METHODS: Adults from an Australian neurology outpatient clinic reporting recurrent vertigo were recruited prospectively and taught to self-record spontaneous and positional nystagmus at home while symptomatic, using miniature video-oculography goggles. Consenting patients with ictal videorecordings and a final unblinded clinical diagnosis of Ménière disease (MD), vestibular migraine (VM), or benign paroxysmal positional vertigo (BPPV) were included. RESULTS: Ictal eye videos of 117 patients were analyzed. Of 43 patients with MD, 40 showed high-velocity spontaneous horizontal nystagmus (median slow-phase velocity [SPV] 39.7°/s; 21 showed horizontal nystagmus reversing direction within 12 hours [24 on separate days]). In 44 of 67 patients with VM, spontaneous horizontal (n = 28, 4.9°/s), upbeating (n = 6, 15.5°/s), or downbeating nystagmus (n = 10, 5.1°/s) was observed; 16 showed positional nystagmus only, and 7 had no nystagmus. Spontaneous horizontal nystagmus with SPV >12.05°/s had a sensitivity and specificity of 95.3% and 82.1% for MD (95% confidence interval [CI] 0.84-0.99, 0.71-0.90). Nystagmus direction change within 12 hours was highly specific (95.7%) for MD (95% CI 0.85-0.99). Spontaneous vertical nystagmus was highly specific (93.0%) for VM (95% CI 0.81-0.99). In the 7 patients with BPPV, spontaneous nystagmus was absent or <3°/s. Lying affected-ear down, patients with BPPV demonstrated paroxysmal positional nystagmus. Median time for peak SPV to halve (T50) was 19.0 seconds. Patients with VM and patients with MD demonstrated persistent positional nystagmus (median T50; 93.1 seconds, 213.2 seconds). T50s <47.3 seconds had a sensitivity and specificity of 100% and 77.8% for BPPV (95% CI 0.54-1.00, 0.64-0.88). CONCLUSION: Patient-initiated vestibular event monitoring is feasible and could facilitate rapid and accurate diagnosis of episodic vestibular disorders.

The human vestibulo-ocular reflex and saccades: normal subjects and the effect of age.

Here we characterize in 80 normal subjects (16-84 yr (means ± SD, 47 ± 19 yr) the vestibulo-ocular reflex (VOR) and saccades in response to three-dimensional head impulses with a monocular video head impulse test (vHIT) of the right eye. Impulses toward the right lateral, right anterior, and left posterior canals (means: 0.98, 0.91, 0.79) had slightly higher mean gains compared with their counterparts (0.95, 0.86, 0.76). In the older age group (>60 yr), gains of the left posterior canal dropped 0.09 and left anterior canals rose 0.09 resulting in symmetry. All canal gains reduced with increasing head velocity (0.02-0.13 per 100°/s). Comparison of lateral canal gains calculated using five published algorithms yielded lower values (~0.80) when a narrow detection window was used. Low-amplitude refixation saccades (amplitude: 1.11 ± 0.98°, peak velocity: 63.9 ± 34.0°/s at 262.0 ± 93.9 ms) were observed among all age groups (frequency: 40.2 ± 23.4%), increasing in amplitude, peak velocity, and frequency in older subjects. Impulses toward anterior canals showed the least frequent saccades and lateral and posterior canals were similar, but lateral canal impulses showed the smallest saccades and the posterior canal showed the largest saccades. Saccade peak-velocity approximate amplitude "main sequence" slope was steeper for the horizontal canals compared with the vertical planes (60 vs. <40°/s per 1°). In summary, we found small but significant asymmetries in monocular vHIT gain that changed with age. Healthy subjects commonly have minuscule refixation saccades that are moderately to strongly correlated with vHIT gain. NEW & NOTEWORTHY Gaze fixation is normally stabilized during rapid "head-impulse" movements by the bisynaptic vestibulo-ocular reflex (VOR), but earlier studies of normal subjects also report small amplitude saccades. We found that with increased age of the subject the vertical VOR became more variable, while in all semicircular canal directions the saccade frequency, amplitude, and peak velocity increased. We also found that the VOR gain algorithm significantly influences values.

Assessment of the Vestibular System: History and Physical Examination.

So common is vertigo that diverse healthcare professionals, from audiologists to orthopedic surgeons, will eventually encounter it in their patients, if not in themselves. So treatable are vestibular disorders that it is an immense advantage to know how to assess the vestibular system. This review summarizes the history and physical examination that will help diagnose common vestibular disorders presenting with vertigo.

The Pro-reparative Engine: Stem Cells Aid Healing by Dampening Inflammation.

PURPOSE OF REVIEW: Stem cells have been proposed as sources for tissue replacement when healing does not occur. These cells could contribute directly to skin structures via differentiation, or via producing trophic factors that would 'educate' the micro-environment to encourage tissue repair. Studies in animals have supported both mechanisms, but translation to humans has been challenged by poor cell survival after transplantation. However, the improvement noted with even transient existence suggests another new possibility, that of suppressing the inflammatory response that limits regenerative healing. Herein, we will propose that this immunomodulatory aspect holds promise for promoting skin healing. RECENT FINDINGS: We have found that stem cell transplantation into wounds can dampen both acute and chronic inflammation, leading to more regenerative-like healing and diminished scarring. SUMMARY: Wound healing could be improved by dampening inflammation both initially to allow for tissue replacement to proceed and late to reduce scarring.

The great escape: How metastases of melanoma, and other carcinomas, avoid elimination.

IMPACT STATEMENT: Cancers kill mainly because metastatic disease is resistant to systemic therapies. It was hoped that newer targeted and immunomodulatory interventions could overcome these issues. However, recent findings point to a generalized resistance to elimination imparted by both cancer-intrinsic and -extrinsic changes to provide survival advantages to the disseminated tumor cells. Here, we present a novel conceptual framework for the microenvironmental inputs and changes that contribute to this generalized therapeutic resistance. In addition we address the issues of experimental systems in terms of studying this phenomenon with their advantages and limitations. This is meant to spur studies into this critical aspect of tumor progression that directly leads to cancer mortality.

Physical Activity and Quality of Life in Cancer Survivors: A Meta-Synthesis of Qualitative Research.

Qualitative research on the impact of physical activity on quality of life (QoL) in adults diagnosed with cancer is accumulating. However, the field of physical activity and cancer survivorship lack a synthesis of this research to reliably understand the implications for future research and practice. The aim of this meta-synthesis was to identify, appraise, and synthesize qualitative research on cancer survivors' perspectives of the impact of physical activity on their QoL. Seven electronic databases were searched for original studies published in English, and reference lists of relevant studies were hand-searched to identify additional studies. Forty studies met eligibility criteria and were included in this meta-synthesis. Study characteristics and major findings were extracted, and findings were summarized, compared, and synthesized. Themes identified in this review revealed that physical activity positively impacted four dimensions of cancer survivors' QoL: physical (e.g., managing the physical consequences of cancer and its treatment), psychological (e.g., evoking positive self-perceptions), social (e.g., feeling understood by others), and spiritual (e.g., redefining life purpose). This meta-synthesis corroborates conclusions from reviews of quantitative research and illustrates that physical activity can be used to improve QoL in adult cancer survivors, regardless of diagnosis (i.e., stage, cancer type) and treatment status. It also provides detailed insight into specific aspects within each dimension of QoL impacted by physical activity from cancer survivors' perspectives, which is important for understanding the meaning and utility of physical activity for them. However, more research is needed to further develop the qualitative evidence base in order to better understand how physical activity impacts on QoL experiences in men, young adults, and adults diagnosed with less common types of cancer at different points along cancer trajectory (i.e., diagnosis, treatment, post-treatment, palliation).

Bedside Assessment of Acute Dizziness and Vertigo.

Dizziness is a common symptom in emergency departments, general practice, and outpatient clinics. Faced with an acutely dizzy patient, the frontline physician must determine whether or not the symptoms are vestibular in origin and, if they are, which vestibular disorder they best fit. A focused history provides useful clues to the likely cause of dizziness, yet it is the clinical examination that yields the final answer. This article summarizes history and examination techniques that are useful in the assessment of acutely dizzy patients and discusses oculomotor signs that accompany common vestibular disorders.