Soluble TNFR1 has greater reproducibility than IL-6 for the assessment of chronic inflammation in older adults: the case for a new inflammatory marker in aging.

Chronic inflammatory pathway activation, commonly referred to as "Inflammaging" or chronic inflammation (CI), is associated with frailty, cognitive and functional decline, and other causes of health span decline in older adults. We investigated the variability of candidate serum measures of CI among community-dwelling older adults selected for mild low-grade inflammation. We focused on serum cytokines known to be highly predictive of adverse health outcomes in older adults (sTNFR1, IL-6) during a short-term (weeks) and medium-term (months) follow-up, as well as immune markers that are less studied in aging but reflect other potentially relevant domains such as adaptive immune activation (sCD25), innate immune activation (sCD14 and sCD163), and the inflammation-metabolism interface (adiponectin/Acrp30) during short-term (weeks) follow up. We found that sTNFR1 was more reproducible than IL-6 over a period of weeks and months short-term and medium-term. The intra-class correlation coefficient (ICC) for sTNFR1 was 0.95 on repeated measures over 6 weeks, and 0.79 on repeated measures with mean interval of 14 weeks, while the ICC for IL-6 was 0.52 over corresponding short-term and 0.67 over corresponding medium-term follow-up. This suggests that sTNFR1 is a more reliable marker of CI than IL-6. This study provides new insights into the reproducibility of serum markers of CI in older adults. The findings suggest that sTNFR1 may be a better marker of CI than IL-6 in this population. Further studies are needed to confirm these findings and to investigate the clinical utility of sTNFR1 in older adults.

Forward and backward locomotion in individuals with dizziness.

The vestibular system plays an important role in locomotion. Individuals with vestibular pathology present with gait abnormalities, which may increase their fall frequency. Backward walking (BW) has been suggested as a predictor of falls in other patient populations; however it has not been studied in individuals with dizziness. Our aims were: (1) to investigate the differences in forward walking (FW) and BW both between and within 3 groups: Healthy controls, individuals with dizziness and vestibular pathology, and individuals with dizziness without vestibular pathology, (2) describe differences in FW and BW between individuals that have fallen and those that have not. We studied 28 healthy controls (mean 53.8 ± 17 years), 21 individuals with pathophysiology of the vestibular system (mean 68.5 ± 13 years), and 18 individuals without a vestibular cause for their dizziness (mean 67.4 ± 17 years). Subjects performed 2 FW and 2 BW trials over the GAITRite walkway. Data on history of falls in the preceding year were collected. We found BW was different to FW within each group. When comparing between groups and correcting for age and gender, only BW velocity (beta=-11.390, p=0.019), cadence (beta=-8.471, p=0.021), step time (beta=0.067, p=0.007) and stride time (beta=0.137, p=0.005) were significantly affected by having dizziness, with no differences in FW characteristics. There were no differences between FW and BW between fallers and non-fallers. BW appears to be a better biomarker than FW for identifying individuals with symptoms of dizziness; though it does not appear to characterize those who fall.

Optimizing ocular vestibular evoked myogenic potential testing for superior semicircular canal dehiscence syndrome: electrode placement.

OBJECTIVE: To compare the sensitivity and specificity of ocular vestibular evoked myogenic potentials (oVEMPs) using 2 electrode montages for the diagnosis of superior canal dehiscence syndrome (SCDS). SUBJECTS: 16 SCDS patients (17 affected-SCDS ears, 15 contralateral-SCDS ears) and 12 controls (24 ears). METHODS: oVEMPs were recorded in response to 500-Hz tone bursts using 2 electrode montages. For both montages the active electrode was placed approximately 5 mm below each eye and a ground electrode on the sternum. For montage 1 (standard), the reference electrode was centered 2 cm below each active electrode. For montage 2, the reference electrode was placed on the chin. RESULTS: For either montage, the separation between oVEMP amplitudes in affected-SCDS ears and controls was significant (p < 0.001), with excellent sensitivity and specificity (>90%). CONCLUSION: oVEMP recordings with the standard montage remain a reliable method for evaluation of SCDS.

Evaluation of a bedside test of utricular function - the bucket test - in older individuals.

CONCLUSION: As a bedside test of subjective visual vertical (SVV), the 'bucket test' has a role as a viable and cost-effective clinical test of unilateral utricular dysfunction in older individuals. OBJECTIVE: To investigate whether the bucket test as a test of the SVV is a valid bedside test of utricular function in older individuals. METHODS: This was a diagnostic validation study at a tertiary academic medical center. Vestibular function was evaluated using sound-evoked cervical and tap-evoked ocular vestibular evoked myogenic potential (cVEMP and oVEMP, respectively) asymmetry ratios, the bucket test of SVV, and the Dizziness Handicap Index (DHI), in 51 older individuals aged 70-95 years. RESULTS: Bucket test scores are correlated in both magnitude and direction with utricle-selective tap-evoked oVEMP asymmetry ratios, but not with sound-evoked cVEMP asymmetry ratios, which are saccule-selective, or with the DHI. Receiver operating characteristics analysis suggests that the bucket test is more specific than sensitive for utricular dysfunction, and a bucket test SVV score of 2° may maximize diagnostic yield relative to the currently accepted score of 3.

Normative results of healthy older adults on standard clinical vestibular tests.

OBJECTIVE: To describe the performance of healthy older adults on common clinical vestibular tests. PATIENTS: Fifty community-dwelling older adults aged 70 and older, with mean age of 77.2 ± 6.1 years and range of 70 to 95 years. INTERVENTION(S): Clinical vestibular tests, including spontaneous and head-shaking nystagmus, head impulse test (HIT), bucket test of subjective visual vertical, modified Romberg test (MRT), and Dizziness Handicap Inventory (DHI). MAIN OUTCOME MEASURE(S): Prevalence of abnormal vestibular tests and DHI score. RESULTS: We observed a 36% and 44% prevalence of abnormal right and left horizontal HIT, respectively. The bucket test was abnormal in 18% of participants; head-shaking nystagmus was present in 2%, and no participant had spontaneous nystagmus. Approximately 68% of participants had abnormal MRT. Abnormal horizontal HIT and MRT were significantly more prevalent among individuals age 80 years and older compared with those age 70 to 79 years (p < 0.05). Mean DHI score was 5.6 ± 11.2, consistent with no self-reported dizziness handicap. CONCLUSION: This study documents the expected performance of normative older adults on vestibular tests commonly administered in the neurotology clinic. We observed a high prevalence of abnormalities on clinical vestibular testing in healthy older adults, although self-perceived dizziness handicap was low. Further studies using newly available clinical testing methods (e.g., video HIT) may identify finer gradations of vestibular function in older individuals and the levels of vestibular loss associated with functional impairment.

Head impulse test abnormalities and influence on gait speed and falls in older individuals.

OBJECTIVE: To assess the prevalence of vestibular dysfunction in older adults using the head impulse test (HIT) and to assess the independent influence of HIT abnormalities on gait speed and fall risk in older individuals. STUDY DESIGN: Cross-sectional study. SETTING: Tertiary care academic medical center. PATIENTS: Fifty community-dwelling individuals age 70 and older. INTERVENTIONS: HIT (abnormal HIT defined as right or left HIT abnormality), visual acuity, monofilament testing, and grip strength. MAIN OUTCOME MEASURES: Gait speed on a 4-meter walk and a history of falls (including number of falls) in the last 1 and 5 years. RESULTS: The participants' mean age was 77 years (range, 70-95 yr); 52% were female subjects. Fifty percent of participants had an abnormal HIT. An abnormal HIT was significantly associated with a 0.23 m/s reduction in gait speed (p = 0.042), 0.44 more falls in the last 1 year (p = 0.047), and a 5-fold increase in the odds of falling in the last 5 years (p = 0.024) in multivariate analyses adjusted for age, sex, and other balance and fall risk factors. CONCLUSION: We observed that half of the community-dwelling older individuals in our study had evidence of vestibular dysfunction, which was significantly associated with gait speed and fall risk in adjusted analyses. Screening for vestibular impairment using the simple HIT and directing targeted vestibular therapy may be important to reduce gait impairment and fall risk in older individuals.

Development and validation of a falls-grading scale.

BACKGROUND AND PURPOSE: The recording of fall events is usually subjective and imprecise, which limits clinical practice and falls-related research. We sought to develop and validate a scale to grade near-fall and fall events on the basis of their severity represented by the use of health care resources, with the goal of standardizing fall reporting in the clinical and research settings. METHODS: Qualitative instrument development was based on a literature review and semistructured interviews to assess face and content validity. We queried older individuals and health care professionals with expertise in the care of patients at risk of falling about clinically important differences to detect and how to optimize the scale's ease of use. To assess the scale's interrater reliability, we created 30 video-vignettes of falls and compared how health care professionals and volunteers rated each of the falls according to our grading scale. RESULTS: We developed the illustrated 4-point Hopkins Falls Grading Scale (HFGS). The grades distinguish a near-fall (grade 1) from a fall for which an individual did not receive medical attention (grade 2), a fall associated with medical attention but not hospital admission (grade 3), and a fall associated with hospital admission (grade 4). Overall, the HFGS exhibited good face and content validity and had an intraclass correlation coefficient of 0.998. CONCLUSION: The 4-point HFGS demonstrates good face and content validity and high interrater reliability. We predict that this tool will facilitate the standardization of falls reporting in both the clinical and research settings.

Association between hearing loss and saccular dysfunction in older individuals.

OBJECTIVE: 1) Describe the association between hearing loss and dysfunction of each of the 5 vestibular end-organs--the horizontal, superior, and posterior semicircular canals; saccule; and utricle--in older individuals. 2) Evaluate whether hearing loss and vestibular end-organ deficits share any risk factors. STUDY DESIGN: Cross-sectional study. SETTING: Academic medical center. PATIENTS: Fifty-one individuals age 70 years or older. INTERVENTIONS: Audiometry, head-thrust dynamic visual acuity (htDVA), sound-evoked cervical vestibular-evoked myogenic potential (cVEMP), and tap-evoked ocular VEMP (oVEMP). MAIN OUTCOME MEASURES: Audiometric pure-tone averages (PTA), htDVA LogMAR scores as a measure of semicircular canal function in each canal plane, and cVEMP and oVEMP amplitudes as a measure of saccular and utricular function, respectively. RESULTS: We observed a significant correlation between hearing loss at high frequencies and reduced cVEMP amplitudes (or reduced saccular function; r = -0.37, p < 0.0001) in subjects age 70 years or older. In contrast, hearing loss was not associated with oVEMP amplitudes (or utricular function), or htDVA LogMAR scores (or semicircular canal function) in any of the canal planes. Age and noise exposure were significantly associated with measures of both cochlear and saccular dysfunction. CONCLUSION: The concomitant decline in the cochlear and saccular function associated with aging may reflect their common embryologic origin in the pars inferior of the labyrinth. Noise exposure seems to be related to both saccular and cochlear dysfunction. These findings suggest a potential benefit of screening individuals with presbycusis-particularly those with significant noise exposure history-for saccular dysfunction, which may contribute to fall risk in the elderly.

Decline in semicircular canal and otolith function with age.

OBJECTIVE: To characterize the physiologic nature of the vestibular dysfunction that occurs with the normative aging process. STUDY DESIGN: Cross-sectional study. SETTING: Tertiary care academic medical center. PATIENTS: Fifty individuals age 70 years and above. INTERVENTIONS: Head thrust dynamic visual acuity testing and cervical and ocular vestibular-evoked myogenic potential (VEMP) testing. MAIN OUTCOME MEASURES: Semicircular canal function measured by head thrust dynamic visual acuity testing in each of the 3 semicircular canal planes, and saccular and utricular function measured by cervical VEMP and ocular VEMP testing, respectively. RESULTS: We observed significant declines in semicircular canal function in each of the canal planes as well as otolith function associated with aging. We found that individuals with impaired horizontal and superior semicircular canal function also were likely to have concomitant deficits in utricular but not saccular function. Overall, we noted that the prevalence of semicircular canal dysfunction was highest followed by saccular then utricular impairment, although we did observe individuals with isolated otolith deficits. CONCLUSION: These data suggest an overall decline in semicircular canal as well as otolith function associated with aging, although the magnitude of impairment was greater for the semicircular canals than the otoliths in this elderly population. A better understanding of the specific vestibular deficits that occur with aging can inform the development of rational screening, vestibular rehabilitation, and fall risk reduction strategies in older individuals.

Second-side surgery in superior canal dehiscence syndrome.

OBJECTIVE: Bilateral superior canal (SC) dehiscence syndrome poses a challenge because bilateral SC dehiscence (SCD) plugging might be expected to result in oscillopsia and disability. Our aims were as follows: 1) to evaluate which symptoms prompted patients with bilateral SCD syndrome (SCDS) to seek second-side surgery, and 2) to determine the prevalence of disabling imbalance and oscillopsia after bilateral SC plugging. STUDY DESIGN: Prospective observational study. SETTING: Tertiary referral center. PATIENTS: Five patients with bilateral SCDS based on history, audiometric and physiologic testing, and computed tomographic findings. This includes all of our patients who have had second-side plugging surgery to date. INTERVENTION(S): Bilateral sequential middle fossa craniotomy and plugging of SCs. MAIN OUTCOME MEASURE(S): Cochleovestibular symptoms, cervical and ocular vestibular-evoked myogenic potential testing, dizziness handicap inventory, short-form 36 Health Survey, dynamic visual acuity testing. RESULTS: The most common symptoms prompting second-side surgery were sound- and pressure-induced vertigo and autophony. Three of the 5 patients reported that symptoms shifted to the contralateral ear immediately after plugging the first side, whereas in 2 patients, contralateral symptoms developed several years after the first SC plugging. Two of 4 patients experienced ongoing oscillopsia after bilateral SCDS surgery; however, all patients reported relief from their SCD symptoms and were glad that they had pursued bilateral surgery. CONCLUSION: In patients with bilateral SCDS, sound- and pressure-induced vertigo most commonly prompted second-side surgery. Despite some degree of oscillopsia after bilateral SCDS surgery, patients were very satisfied with second-side surgery, given their relief from other SCDS symptoms.

Magnesium for treatment of asthma in children.

QUESTION: Magnesium is considered adjuvant therapy for moderate to severe asthma exacerbations in adults, but can it be used to treat children? ANSWER: Magnesium seems to be beneficial in the treatment of moderate to severe asthma in children. It is a safe drug to administer, but there have been minor side effects reported, such as epigastric or facial warmth, flushing, pain and numbness at the infusion site, dry mouth, malaise, and hypotension. Owing to its bronchodilating and anti-inflammatory effects, magnesium is an encouraging adjuvant therapy for pediatric patients who do not respond to conventional treatment in acute severe exacerbations. Future studies should focus on establishing the optimal dosage for maximal benefits and the best route of administration. Magnesium should also be considered as a prophylactic treatment.