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Objective There is emerging evidence that individual levels of sensory sensitivity may impact treatment outcomes for people recovering from burn injuries. For example, individuals with higher levels of sensory sensitivity were less adherent with compression garment wear, often used for scar management. The purpose of this study was to characterise sensory patterns for a sample of burn-injured patients as a cohort, using normative data as the reference. As different patterns of sensory processing can have implications clinically, understanding this at the cohort level may provide valuable insight for therapy. Method This was a secondary analysis of data collected during a cross-sectional study. Adults (N=117) attending the Professor Stuart Pegg Adult Burns Unit outpatient clinic completed the Adolescent/Adult Sensory Profile and the following quantitative sensory tests: two-point discrimination; mechanical detection threshold; and pressure pain threshold. Results Compared to matched normative data, burn-injured patients reported higher levels of sensory sensitive and avoiding patterns, and experienced lower detection thresholds for touch and pain. Conclusions Higher reports of sensory sensitivity and sensory avoiding, and lower thresholds for touch and pain, have been correlated with tactile defensiveness. Tactile defensiveness has been associated with social withdrawal and isolation, all of which could contribute to decreased engagement in therapy. The ways in which these sensory characteristics impact on burn-related treatments, such as compression garment adherence, warrant further investigation.

Objective Next to olfactory function, the nose can also perceive chemestetic sensations mediated by the trigeminal nerve. While olfactory dysfunction as a symptom of COVID-19 is well described, there has been little research on the limitation of other nasal sensory inputs due to SARS-CoV-2 infection. The aim of this study was to determine possible limitations of nasal chemesthesis after COVID-19 infection by a psychophysiological diagnostic tool. Methods In 65 patients with a PCR-confirmed, former COVID-19 disease, olfaction was tested by means of a sniffin' sticks test, tasting by taste sprays and chemesthesis with a menthol dilution series. The subjective self-assessment of the patients was recorded via a questionnaire. Results We found a restriction of nasal chemesthesis and the extent correlated with the loss of smell, as well as with the values of the taste score, but not with subjective self-assessment. Conclusion Not only the ability to smell and taste, but also nasal chemesthesis is affected by COVID-19.

AimImpaired vibrotactile sense, mirroring diabetic peripheral neuropathy, is present among children and adolescents with type 1 diabetes. This study aims to re-examine the vibrotactile sense of paediatric type 1 diabetes subjects in order to evaluate any alterations in the vibrotactile sense over time.MethodsA VibroSense Meter I device was used to determine the vibrotactile perception thresholds (VPTs) for seven frequencies from the pulp of index and little fingers and for five frequencies from metatarsal heads one and five on the sole of the foot, of 37 children and adolescents with type 1 diabetes, previously examined in a larger cohort. Subjects were followed up after a median time of 30 months. Z-scores of VPTs were calculated using previously collected normative data.ResultsVPTs improved over time at low frequencies (especially 16 Hz) on the foot, while not being statistically significant different on the rest of the frequencies, either on hand or foot. VPTs were not correlated to HbA1c.ConclusionA mid-term follow-up of vibrotactile sense in paediatric subjects with type 1 diabetes shows a conceivable normalization of previously impaired vibrotactile sense on some frequencies on the foot, indicating that vibrotactile sense might fluctuate over time. (Less)

ObjectiveTo assess the prevalence of abnormal rhinological findings in a Sjögren's syndrome population.MethodsA cohort-matched, prospective, cross-sectional, observational study was conducted. Sixty-seven subjects (30 patients and 37 controls) were enrolled. Rhinological assessment including smell threshold was evaluated using a standardised, validated clinical test as part of a larger study.ResultsSmell thresholds were –4.4 and –5.4 in the Sjögren's syndrome and control groups, respectively (p = 0.001). Hyposmia (threshold values of less than −4.5) was demonstrated in the Sjögren's syndrome group (47 per cent). Smell was negatively correlated with age (p = 0.040). Nasal septal perforation was noted in 3 Sjögren's syndrome patients (10 per cent) and nasal mucosal dryness in 10 patients (33 per cent), but none of the control group were affected.ConclusionHyposmia in Sjögren's syndrome was demonstrated using the Smell Threshold Test. Nasal septal perforation and nasal mucosa dryness were also noted in patients with Sjögren's syndrome. A diagnosis of Sjögren's syndrome should be considered and investigated in smell deprivation and/or nasal septal perforation patients.

Objectives/hypothesis To develop a method for threshold estimation of the laryngeal adductor reflex (LAR) response using Cheung-Bearelly monofilaments. Study design Cross-sectional. Methods Twenty-two healthy adults (12 men, 10 women) were tested for LAR response outcome using 30 mm 5-0 and 4-0 nylon monofilaments. Tactile stimuli were delivered to the aryepiglottic (AE) fold and medial pyriform sinus (MPS). Dichotomous classifier features and performance (area under the curve (AUC)), the LAR response outcome agreement and disagreement matrix, and test-retest reliability were examined. From those data, a test protocol that would minimize patient burden to estimate the LAR triggering threshold was formulated. Results Classifier performance of 5-0 monofilament stimulation of the AE fold (sensitivity = 0.63, specificity = 0.63, PPV = 0.74, NPV = 0.25) and MPS (sensitivity = 0.45, specificity = 0.77, PPV = 0.74, NPV = 0.23,) was slightly below that of 4-0 monofilament stimulation of the AE fold (sensitivity = 0.82, specificity = 0.50, PPV = 0.82, NPV = 0.50) and MPS (sensitivity = 0.84, specificity = 0.64, PPV = 0.90, NPV = 0.56), based on AUC. LAR response outcome agreement for 5-0 and 4-0 stimulations was high (93%) for 5-0 positive response, but low (29%) for 5-0 negative response. Aesthesiometer test-retest reliability for LAR response outcome was excellent (Cronbach's alpha = 0.97). Conclusions Threshold estimation of the LAR response may be operationalized by adopting a decision tree protocol. For negative LAR response to initial 5-0 monofilament stimulation and positive response to subsequent 4-0 monofilament stimulation, the higher threshold is confirmed. Positive LAR response to 5-0 or 4-0 monofilament stimulation is expected in over 90% of asymptomatic adults. Negative LAR response to 4-0 monofilament stimulation identifies patients at risk for laryngopharyngeal hyposensitivity. Level of evidence 3b Laryngoscope, 2021.

Introduction Smell disorders are common in the general population and occur e.g., after infections, trauma or idiopathically Treatment strategies for smell loss range from surgery, medication to olfactory training, depending on the pathology, but they are limited This study examined the effect of acupuncture on olfactory function. Methods Sixty patients with smell loss following infections of the upper respiratory tract were included in this investigation Half of the study group were randomly assigned to verum acupuncture and the other half to sham acupuncture Olfaction was measured by means of the “Sniffin’ Sticks” test battery (odour threshold, discrimination and identification). Results Compared to sham acupuncture, verum was associated with an improvement of smell function as measured by the TDI score (p = 0.039) The improvement was largely determined by improvement in odour discrimination, and was significantly better in patients with a shorter duration of the disorder. Conclusion The present results suggest that acupuncture is an effective supplementary treatment option for patients with olfactory loss.

Objective To investigate the effects of perturbation-based pinch task training on the sensorimotor performance of the upper extremities of patients with chronic stroke via a novel vibrotactile therapy system. Design A single-blinded randomized controlled trial. Setting A university hospital. Participants Patients with chronic stroke (N=19) randomly assigned into either an experimental group or a control group completed the study. Interventions In addition to 10 minutes of traditional sensorimotor facilitation, each participant in the experimental group received 20 minutes of perturbation-based pinch task training in each treatment session, and the controls received 20 minutes of task-specific motor training twice a week for 6 weeks. Main Outcome Measures The scores for the primary outcome, Semmes-Weinstein monofilament (SWM), and those for the secondary outcomes, Fugl-Meyer Assessment (FMA), amount of use, quality of movement (QOM) on the Motor Activity Log (MAL) scale, and box and block test (BBT), were recorded. All outcome measures were recorded at pretreatment, post treatment, and 12-week follow-up. Results There were statistically significant between-group differences in the training-induced improvements revealed in the SWM results (P=.04) immediately after training and in the BBT results (P=.05) at the 12-week follow-up. The changes in muscle tone and in the QOM, SWM, and BBT scores indicated statistically significant improvements after 12 sessions of treatment for the experimental group. For the control group, a significant statistical improvement was found in the wrist (P Conclusions This study indicated that the perturbation-based pinch task training has beneficial effects on sensory restoration of the affected thumb in patients with chronic stroke.

The International Standard Organization (ISO) standard 13091-1 describes methods and procedures for performing the vibrotactile perception threshold (VPT) testing to diagnose changes in tactile sensory function associated with occupational exposures. However, the VPT test also has been used in the diagnosis of peripheral neuropathies associated with a number of disorders. This review examines the VPT test, variations in procedures that have been used, as well as disorders and diseases in which this test has been reliable for the detection of sensory changes. Mechanisms potentially underlying the changes in VPTs are also discussed along with procedural and subject/patient factors that may affect the interpretation of test results. Based upon the review of the literature, there are also suggestions for where additional research might improve the administration of this test, depending upon the subject/patient population and interpretation of data.

Purpose The present study aimed to establish a test battery for the clinical assessment of retronasal odor thresholds and retronasal odor identification. Study design Prospective case–control series. Methods Sixty participants (36 women, 24 men, mean age 37.6 ± 19.4 years) were enrolled in this study; 36 were healthy controls and 24 were patients with olfactory dysfunction. Orthonasal olfactory function was assessed with the “Sniffin’ Sticks” test battery. Retronasal olfaction was assessed with oral odorant delivery using special containers for threshold function, and with oral tasteless powders for odor identification. Results Retronasal and orthonasal olfaction were significantly correlated for threshold scores, identification score, and the sum of threshold and identification score (TI score). Validity analyses showed that the retronasal TI score was able to discriminate between healthy controls and patients with olfactory dysfunction. Conclusions Normosmic participants can be distinctly differentiated from patients with olfactory dysfunction using a valid test battery comprised of retronasal threshold and identification tests. Based on the current findings, we advocate a TI score of 16 as a cut-off between patients and controls. Therefore, TI scores of 17 and above would indicate retronasal normosmia.

Controlling posture requires continuous sensory feedback about body motion and orientation, including from the vestibular organs. Little is known about the role of tilt vs. translation vs. rotation vestibular cues. We examined whether intersubject differences in vestibular function were correlated with intersubject differences in postural control. Vestibular function was assayed using vestibular direction-recognition perceptual thresholds, which determine the smallest motion that can be reliably perceived by a subject seated on a motorized platform in the dark. In study A, we measured thresholds for lateral translation, vertical translation, yaw rotation, and head-centered roll tilts. In study B, we measured thresholds for roll, pitch, and left anterior-right posterior and right anterior-left posterior tilts. Center-of-pressure (CoP) sway was measured in sensory organization tests (study A) and Romberg tests (study B). We found a strong positive relationship between CoP sway and lateral translation thresholds but not CoP sway and other thresholds. This finding suggests that the vestibular encoding of lateral translation may contribute substantially to balance control. Since thresholds assay sensory noise, our results support the hypothesis that vestibular noise contributes to spontaneous postural sway. Specifically, we found that lateral translation thresholds explained more of the variation in postural sway in postural test conditions with altered proprioceptive cues (vs. a solid surface), consistent with postural sway being more dependent on vestibular noise when the vestibular contribution to balance is higher. These results have potential implications for vestibular implants, balance prostheses, and physical therapy exercises. NEW & NOTEWORTHY Vestibular feedback is important for postural control, but little is known about the role of tilt cues vs. translation cues vs. rotation cues. We studied healthy human subjects with no known vestibular pathology or symptoms. Our findings showed that vestibular encoding of lateral translation correlated with medial-lateral postural sway, consistent with lateral translation cues contributing to balance control. This adds support to the hypothesis that vestibular noise contributes to spontaneous postural sway.

Objectives: Hamstring injuries in athletes can lead to significant time away from competition as a result of persistent posterior thigh pain. These cases are often difficult to treat as the state of the tissues alone cannot explain symptoms. In non-athletic populations with persistent pain, disruptions to tactile, proprioceptive, and spatial cortical representations exist, which has led to promising brain-based treatments.Here, we explored whether athletes with persistent posterior thigh pain also display impairments in these cortical representations.Design: Cross-sectional study.Methods: Fourteen male professional athletes with persistent posterior thigh pain (‘Patients’) and 14pain-free age, sport, body mass index and level-matched controls (‘Controls’) participated. The tactile cortical representation was assessed using two-point discrimination (TPD) threshold and accuracy of tactile localisation; the proprioceptive cortical representation was assessed using a left/right judgement task; spatial processing was assessed using an auditory detection task. Results: TPD thresholds were similar for Patients and Controls (p = 0.70). Patients were less accurate at localising tactile stimuli delivered to their affected leg, slower to make left/right judgements when the lower limb image corresponded to the side of their affected leg, and less accurate at detecting auditory stimuli delivered near their affected leg, when compared to their healthy leg or to the leg of Controls(p < 0.01 for all). Conclusions: Leg-specific tactile, proprioceptive, and spatial processing deficits exist in athletes with persistent posterior thigh pain. That these processing deficits exist despite rehabilitation and normal tissue healing time suggests they may play a role in the persistence of posterior thigh pain. Refereed/Peer-reviewed

Background: Few odor tests have been developed for children. Objectives: The aim of the present study was to develop and validate a simple and quick olfactory test to evaluate odor identification and threshold in a Spanish pediatric population. Methods: The Pediatric Barcelona Olfactory Test-6 (pBOT-6) consisted of a set of 6 odorants for a forced choice identification test and a 6-dilution phenyl ethyl alcohol geometric series for the threshold test. The pBOT-6 was compared with the Universal Sniff test (a validated international pediatric smell test) in 131 healthy Spanish volunteers aged 6-17 years. A Bland-Altman plot was used to determine the agreement between the 2 tests. Reliability was analyzed in 15 volunteers using the intraclass correlation coefficient. Normative data were obtained, and 8 children diagnosed with subjective loss of smell were tested for validation. Results: The Bland-Altman analysis demonstrated a minimal bias of –1.71% with upper and lower limits of agreement of –31.1% and 27.6%, respectively. The intraclass correlation coefficient was 0.83 (95%CI, 0.6-0.96) for the identification test and 0.73 (95%CI, 0.36-0.9) for the threshold test, with excellent and good consistency between measurements over time. Mean pBOT-6 scores were significantly higher in healthy volunteers than in patients with loss of smell. Discrimination between normosmia and loss of smell was achieved with a sensitivity of 96.9% and a specificity of 100%. Conclusions: pBOT-6 offers an effective and fast method that is useful in clinical routine to distinguish, with high sensitivity and specificity, between pediatric patients with normosmia and those with loss of smell.

INTRODUCTION Normal bowel function requires intact sensory pathways. Diminished rectal sensation (rectal hyposensitivity [RH]) is associated with constipation, although its clinical importance remains unclear. METHODS Consecutive patients (aged 18-80) attending a tertiary center (2004-2016) for investigation of refractory functional constipation (Rome IV core criteria defined, applied post hoc) were included. Patients completed a clinical symptom questionnaire and underwent anorectal physiologic investigations, including rectal sensory testing (balloon distension) to determine 3 well-established sensory thresholds. Multivariate regression analyses were performed to evaluate associations between RH, symptomology, and allied physiologic investigations. RESULTS Of 2,876 patients meeting inclusion criteria, 722 (25%) had RH based on ≥1 elevated sensory thresholds (0: n = 2,154 [74.9%]; 1: n = 327 [11.4%]; 2: n = 209 [7.3%]; and 3: n = 186 [6.5%]). A linear relationship existed between increasing number of elevated sensory thresholds and constipation severity (Cleveland Clinic constipation score: mean difference per threshold [95% confidence interval] 0.69 [0.48-0.90]; P < 0.001). Several symptoms were significantly (P < 0.05) associated with RH including: infrequent defecation (odds ratio 1.29 [1.17-1.42]), painful evacuation (1.15 [1.05-1.27]), prolonged toileting (1.14 [1.05-1.24]), and digitation or enema use (1.18 [1.08-1.30]). On defecography, a "functional" evacuation disorder was also associated with RH (1.37 [1.25-1.50], P < 0.001), as was megarectum (2.52 [2.08-3.05], P < 0.001). DISCUSSION RH occurs in 25% of patients with refractory functional constipation. Increased number of elevated sensory thresholds is associated with more severe constipation phenotype. These data, in the largest study to date, provide for the first time evidence to show that RH is a major pathophysiologic mechanism in constipation, with recognized clinical impact (http://links.lww.com/AJG/B765).(Equation is included in full-text article.).

Introduction To better understand the pathophysiology of isolated head tremor, we investigated somatosensory temporal discrimination threshold (STDT) and dopaminergic neurotransmission with 123I-FP-CIT (DAT-SPECT) in patients with isolated head tremor, as well as potential correlations with their clinical features. Methods We enrolled 14 patients with isolated head tremor who underwent clinical examination, STDT testing, and DAT-SPECT. Results We found normal radiotracer uptake in both striata as assessed with DAT-SPECT examination, but higher STDT values in patients as compared to healthy subjects. No significant correlations emerged between STDT values, specific binding ratios of radiotracer uptake, and demographic or clinical features. Conclusion Our study found normal radiotracer uptake with DAT-SPECT examination, suggesting dopaminergic neurotransmission integrity in patients with isolated head tremor. Patients with isolated head tremor exhibited an abnormally elevated STDT. Both results support the hypothesis that isolated head tremor should be considered a form of dystonia.

Playing the piano involves rapid and precise upper limb movements, which require seamless integration of the proprioceptive and motor systems. In this study, we comprehensively assessed active and passive proprioception and different domains of motor function in young pianists, aiming to understand how their proprioceptive and motor functions are improved. Fifty-seven participants, including seventeen 11- to 12-yr-old (young) pianists, 20 children, and 20 adults, were included. The children in the pianist group had received piano training for 6 yr, whereas the children and adults in the control groups had no previous experience with instrumental training. All participants performed a psychophysical discrimination threshold hunting task and an ipsilateral joint position reproduction task, both of which measured the position sense acuity of the wrist. Their motor function was evaluated by the Movement Assessment Battery for Children, 2nd edition. The results revealed that the young pianists showed a significantly lower position sense discrimination threshold (31%) and fewer joint position reproduction errors (49%) than the nontrained children. Second, a higher level of manual dexterity, but not of ball skills or balance, was found in the young pianist group. Third, a higher proprioceptive acuity (i.e., decreased position sense discrimination threshold) significantly correlated with higher manual dexterity. This study documents that a high wrist position sense is a common characteristic among young pianists. The increased upper limb position sense acuity is correlated with better manual dexterity, suggesting that piano practice may benefit untrained fine motor skills in children.

This study aims to evaluate the application of the University of Pennsylvania Smell Identification Test (UPSIT) in Thailand, as well as to conduct an odor detection threshold test using phenyl ethyl alcohol and a 30-odor smell identification test.This study was conducted from May 2019 to March 2020. We included healthy volunteers without any olfactory complaints. All participants underwent the UPSIT, an evaluation of odor detection threshold, and a 30-odor smell identification test.One hundred fifty participants were included in our study. The overall mean score on the UPSIT was 26.04 ± 6.59 points and ranged from 9 to 39.7. For participants aged under 60 years, the mean UPSIT score was 29.08 ± 4.67 points, while the mean score of those 60 years of age and over was 19.20 ± 4.97 points (mean difference of 9.88 points), a difference that was statistically significant (95% CI 8.23 to 11.53, p0.0001). The mean lowest log value on the odor detection threshold test was -7.12 ± 1.64. This was -7.53 ± 1.05 in participants under 60 years of age and -6.20 ± 2.27 in those 60 years of age and over (mean difference of 1.33; 95% CI 0.80 to 1.86, p0.0001). Items in the 30-odor smell identification test with correct response rates greater than 70% included fish sauce, banana, coffee, patchouli water, coconut, lemongrass, orange, ammonia, vinegar, tea leaf, Thai perfume, jasmine, pandan, curry, lime, durian, cola, corn, pineapple, strawberry, and grape.This study identified the odor detection threshold, UPSIT scores, and suitable odors to use in smell identification in a Thai population.

Caffeine has been demonstrated to enhance olfactory function in rodents, but to date, the sparse research in humans has not shown any equivalent effects. However, due to the methodological nature of those human studies, a number of questions remain unanswered, which the present study aimed to investigate. Using a double-blind experimental design, participants (n = 40) completed baseline mood measures, standardised threshold and identification tests and were then randomly allocated to receive a capsule containing either 100 mg of caffeine or placebo, followed by the same olfactory tests and mood measures. Results revealed that despite a trend toward elevated arousal following caffeine for habitual caffeine consumers, there were no changes in odour function. In contrast, for non-caffeine consumers, caffeine acted to enhance odour (threshold) sensitivity but reduce odour identification. Overall, these findings demonstrate a complex profile of effects of caffeine on odour function and, given the evidence from the wider caffeine literature, it is proposed that the effects of caffeine might be limited to older populations.

This study evaluates among middle-aged subjects with obesity the prevalence of olfactory impairment (OI) with respect to normative values and its correlation with body composition, cognition, sleep quality, and inflammation. In 60 (31 women, 29 men) volunteers with a body mass index ≥ 30 to ≤ 40 kg/m2, aged ≥ 50 to ≤ 70 years, we assessed olfaction by the Sniffin’ Stick test. We measured anthropometrics, body composition and metabolic profiles and evaluated cognition by the MiniMental State Examination (MMSE) and sleep disturbances by the Insomnia Severity Index (ISI). Patients were classified into two groups according to a total olfactory score (odor Threshold, Discrimination, Identification, TDI) below or above the 25th percentile from age and gender-adjusted normative data. Overall, 25 subjects (42%) had OI (TDI

Variability in human olfactory sensitivity has been attributed to individual-level factors such as genetics, age, sex, medical history of infections and trauma, neurogenerative diseases, and emotional disorders. Scarce evidence exists on the cross-cultural variation in olfactory sensitivity. Hence, we performed 2 studies to estimate the variability in olfactory threshold as a function of location and environment. Study 1 involved 11 laboratories from 4 continents (N = 802). In each location, in a designated laboratory, approximately 80 subjects underwent olfactory sensitivity testing with custom-made tests with eucalyptol and phenylethanol (PEA) odors. Tests were based on the Threshold subtest of the Sniffin' Sticks battery. In Study 2, we compared olfactory sensitivity and suprathreshold perception of PEA and eucalyptol in 2 Chinese (N = 160) and 2 Indian (N = 92) populations-one based in their native country and the other in Germany. Both studies present large-scale evidence that olfactory sensitivity varies as a function of geographical location and suggest that environmental factors play an important role in shaping olfactory sensitivity and suprathreshold olfactory perception. We delineate further steps necessary to identify specific factors underlying uncovered variability and the relationship between olfactory sensitivity and suprathreshold odor perception. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The exposure-driven olfactory compensation associated with sensory loss is likely to be observed in assessment of food-related dangers. Therefore, in the current study we tested the hypothesis that olfactory compensation occurs in the case of protection from food-related hazards. We compared thresholds for detection of an unpleasant rotten food odor (fermented fish sauce) in four groups of subjects: blind subjects (n = 100), sighted controls (n = 100), deaf subjects (n = 74) and hearing controls (n = 99). Overall, we observed no significant differences in smell acuity between the blind and deaf groups and their matched control samples. However, the sensory deprived subjects assessed their sensitivity as higher than did control groups. The present study is yet another example of research among large samples of sensory deprived individuals that shows no evidence of olfactory compensation. This result is consistent with a growing number of studies suggesting no sensory compensation in simple, absolute sensitivity tasks.

INTRODUCTION: Tibial nerve entrapment is highly prevalent in diabetic subjects, resulting in significantly more neuropathic complaints and concomitant sensory disturbances. The study aim was to assess the impact of tarsal tunnel syndrome (TTS) and sensory loss at baseline on incident diabetic foot ulceration (DFU) in diabetic patients, since decompressing the tibial nerve might change the natural history of the disease.METHODS: In this study, 113 subjects with TTS (69 bilateral, 23 left-sided and 21 right-sided) participating in the prospective Rotterdam Diabetic Foot Study were compared to 303 diabetic controls without TTS, regarding incident DFU. Kaplan-Meier analysis and Cox's regression analysis were used to determine the independent hazard of baseline variables for new DFU.RESULTS: The median observation period was 836.5 days (IQR, 459-1077.8). In bilateral TTS, 17.4% (95% CI: 8.4-26.3%) of subjects experienced DFU versus 8.3% (95% CI: 5.1-11.6%) in controls (left or right) during follow-up (p = 0.0036). In left-sided TTS, no subjects versus 6.2% (95% CI: 3.4-9.0%) in controls had DFUs (p = 0.243). Incident ulceration was seen in 14.3% (95% CI: -0.7% to -29.3%) of right-sided TTS subjects versus 4.1% (95% CI: 1.5-6.3%) in controls (p = 0.034). Besides HbA1c, diminished sensation at the hallux independently increased the risk of ulceration, in patients with (HR: 4.692, p = 0.003) and without (HR: 2.307, p = 0.002) prior DFU.DISCUSSION: Elevated sensory thresholds in TTS render diabetic patients at a higher risk for DFU. With effective surgery, TTS is likely to be an amenable factor to potentially prevent diabetic foot disease and thereby reduce amputation risk.LEVEL OF EVIDENCE: II.

Background While valid and reliable olfactory tests have been developed for children aged >5 years, olfactory testing has not systematically been evaluated in younger children. The aim of this study was to evaluate the reliability and validity of the “U-Sniff” odor identification test in children aged 3–6 years. Methods We included 160 healthy children (age range 3–6 years) and 14 congenitally anosmic children. Participants were investigated in two identical sessions. The “U-Sniff” test was used to evaluate olfactory function. A picture identification test (PIT) and the Kasel-Concentration-Task (KKA) were administered to identify factors influencing odor identification performance. Results Age significantly influenced odor identification performance, with older children achieving higher scores. PIT and KKA scores correlated positively with odor identification scores. The “U-Sniff” test demonstrated a high test–retest reliability (r160 = 0.75, p Conclusions The “U-Sniff” test is feasible for children starting at age 3 years. In children aged ≥4 years, it is a reliable and valid method to distinguish between normal olfactory function and anosmia. Impact Olfactory testing is reliable and valid starting at an age of 4 years. The study adds a systematic evaluation of olfactory testing in young children. Results of this study are especially interesting for clinicians in the diagnosis of olfactory dysfunction.

Quantitative sensory testing (QST) is a psychophysical test used to quantify somatosensory sensation under normal or pathological conditions including osteoarthritis (OA).OBJECTIVE: This study aimed to conduct a systematic review and meta-analysis of studies using QST in healthy and osteoarthritic cats, registered at Systematic Review Research Facility (#26-06-2017).DESIGN: Hierarchical models with random intercepts for each individual study extracted through the systematic review were fit to subject-level data; QST measures were contrasted between healthy and osteoarthritic cats. Four bibliographic databases were searched; quality and risk of bias assessment were performed using pre-established criteria.RESULTS: Six articles were included; most were of high quality and low risk of bias. Punctate tactile threshold (n=70) and mechanical temporal summation (n=35) were eligible for analysis. Cats with OA have lower punctate tactile threshold [mean difference (95%HDI): -44 (-60; -26) grams] and facilitated temporal summation of pain [hazard ratio (95%HDI): 5.32 (2.19; 14) times] when compared with healthy cats. The effect of sex and body weight on sensory sensitivity remained inconclusive throughout all analyses. Due to the correlation between age and OA status, it remains difficult to assess the effect of OA on sensory sensitivity, independently of age.CONCLUSIONS: Clear and transparent reporting using guidelines are warranted. Similar to people, centralized sensitization is a feature of OA in cats. Future studies should try to elucidate the age effect on feline OA. Research with natural OA in cats is promising with potential to benefit feline health and welfare, and improve translatability to clinical research.

Previous work has shown that motion perception in school-age children is similar to that of adults for fast speeds but is immature at slow speeds for stimuli presented in the central visual field. This study examined whether visual field location affects this developmental pattern. We measured left/right and up/down global motion direction discrimination for fast and slow speeds in 7- to 10-year-old children and in adults with stimuli presented to upper, central, or lower visual fields. For left/right direction discrimination, children showed significantly higher (worse) coherence thresholds than adults for slow, but not fast, speeds in the central visual field. In the upper and lower visual fields, children showed significantly higher coherence thresholds than adults for both speeds. For up/down direction discrimination, children showed similar performance to adults for the central visual field. In the upper and lower visual fields, children performed significantly worse than adults; this finding was speed-tuned only for the lower visual field. Thus, children show immature global motion perception in the periphery even when performance in central vision is adult-like. These results enrich our understanding of motion perception development in children with typical vision.

Vestibular perceptual thresholds measure vestibular sensory and perceptual noise by quantifying how small of a passive self-motion an individual is able to reliably perceive. Vestibular thresholds have clinical and operational relevance, as they are elevated in vestibular migraine patients, and even healthy individuals with higher (i.e., worse) thresholds have degraded balance. Vestibular thresholds have been quantified across a range of frequencies (motion durations) for rotations and translations, with differences identified for different motion directions (e.g., up/down thresholds are higher than those for left/right motions). While roll tilt thresholds have been well quantified, pitch tilt thresholds have not. Here we aim to quantify pitch tilt thresholds across a range of frequencies and test whether they are higher than in those for roll tilt. In ten normal subjects, we found pitch tilt thresholds at 0.15, 0.2, 0.5, and 1 Hz averaged 1.66, 1.61, 0.99, 0.51 degrees, respectively. Using a general linear model, we found subjects' pitch tilt thresholds were slightly, but significantly, higher than their roll tilt thresholds across all frequencies tested. These differences were approximately 10% at 0.15, 0.2, and 1 Hz and 3% at 0.5 Hz. Pitch tilt thresholds exhibited a similar frequency response as in roll tilt (decreasing a higher frequencies). They also had substantial inter-individual variability, which correlated across pitch tilt frequencies and between pitch and roll tilt thresholds. We discuss why pitch tilt thresholds might be higher, including the pitched-up orientation of the utricular plane of the otoliths, compared to previous studies, and discuss functional implications.

Introduction Fatigue is a recognized manifestation of immune-mediated neuropathies, but its causes and implications are unclear. In this study, we explored the correlates of fatigue among a number of clinical parameters in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) to better understand potential contributing factors and resulting consequences. Methods Twenty-six clinically stable patients with CIDP underwent assessments of motor and sensory function, disability, quality of life, and depression and anxiety. Experienced fatigue was assessed by using the Rasch-built Fatigue Severity Scale and the Checklist of Individual Strength. Results The two fatigue scales provided evidence of significant intercorrelation. Only depression scores and grip strength predicted experienced fatigue levels in multivariate regression analyses. Fatigue scores inversely correlated with strength, sensory, disability, and quality of life scores. Discussion Experienced fatigue is likely multifactorial in CIDP, with both physical and neuropsychiatric components. Fatigue is associated with lower functional and quality-of-life outcomes in CIDP.

Objectives To evaluate long-term olfactory outcomes in patients who underwent pituitary surgery through the endoscopic endonasal transsphenoidal approach (EETSA) by T&T olfactometer. Methods We retrospectively reviewed 26 patients who underwent pituitary surgery via EETSA. Olfactory function was assessed by T&T olfactometer before and 6 months after surgery. The mean of recognition thresholds for five different odorants was used. The change in the mean recognition threshold values was evaluated in the entire cohort and the subgroup analysis was performed according to the age, sex, past history of pituitary surgery (primary surgery or revision surgery), histopathology (non-functioning adenoma (NFA) or functioning adenoma (FA)), reconstruction procedure (rescue flap or nasoseptal flap), and superior turbinate management (preserved or resected). Results Of the 26 patients (12 men and 14 women, median age 53 years), 21 patients were newly diagnosed with pituitary gland tumor (16 NFAs, 5 FAs) and the remaining 5 were diagnosed with recurrent pituitary gland tumor (4 NFAs and 1 FA). In the whole cohort, the mean recognition threshold values of T&T olfactometer significantly improved after surgery (P = 0.01). Thirteen out of 26 patients (50%) showed olfactory improvement, whereas only 3 (12%) showed deterioration. In the subgroup analysis, olfactory function outcomes were not significantly different between the subgroups with respect to the age, sex, past history of pituitary surgery, histopathology, reconstruction procedure, or superior turbinate management. The olfactory function tended to worsen in the revision surgery group compared to that in the primary surgery group, but not significantly (P = 0.06). Conclusions The olfactory function was improved or maintained after pituitary surgery via EETSA in 88% of patients, indicating the benefits of low invasiveness of our surgical treatment. On the other hand, three patients (12%) demonstrated deterioration of olfactory function, suggesting that the risk of postoperative olfactory dysfunction should be informed to patients.

Visual functions decline with age, but how aging degrades visual functions remains controversial. In the current study, the mechanisms underlying age-related visual declines were examined psychophysically. We developed an efficient method to quickly explore contrast sensitivity as a function of nine spatial frequencies at three levels of external noise in both young and old subjects. Fifty-two young and twenty-six old subjects have been screened for ophthalmological and mental diseases and participated in the experiment. Contrast sensitivity varied significantly with spatial frequency, age, and level of external noise. By adopting a nonlinear observer model, we decomposed contrast sensitivity into inefficiencies in internal additive noise, internal multiplicative noise, perceptual template gain, and/or system non-linearity. Model analysis revealed that aging impacts both internal additive noise and perceptual template gain, and such age-related degradation is tuned to spatial frequency, which is also a good predictor to discriminate old from young. The quick characterization of contrast sensitivity functions at different noise levels and the accompanying analysis developed in the current study may have profound application in other clinical populations.

Quantitative sensory testing (QST) is used to evaluate the function of the somatosensory system in dogs by assessing the response to applied mechanical and thermal stimuli. QST is used to determine normal dogs' sensory thresholds and evaluate alterations in peripheral and central sensory pathways caused by various disease states, including osteoarthritis, spinal cord injury, and cranial cruciate ligament rupture. Mechanical sensory thresholds are measured by electronic von Frey anesthesiometers and pressure algometers. They are determined as the force at which the dog exhibits a response indicating conscious stimulus perception. Hot thermal sensory thresholds are the latency to respond to a fixed or ramped temperature stimulus applied by a contact thermode. Following a consistent protocol for performing QST and paying attention to details of the testing environment, procedure, and individual study subjects are critical for obtaining accurate QST results for dogs. Protocols for the standardized collection of QST data in dogs have not been described in detail. QST should be performed in a quiet, distraction-free environment that is comfortable for the dog, the QST operator, and the handler. Ensuring that the dog is calm, relaxed, and properly positioned for each measurement helps produce reliable, consistent responses to the stimuli and makes the testing process more manageable. The QST operator and handler should be familiar and comfortable with handling dogs and interpreting dogs' behavioral responses to potentially painful stimuli to determine the endpoint of testing, reduce stress, and maintain safety during the testing process.

Background: Odor identification is related to odor naming, which is more of a verbal than an olfactory sensory task. Linguistic functions in right-handers are typically lateralized to the left hemi...

The perception of an event is strongly influenced by the context in which it occurs. Here, we examined the effect of a rhythmic context on detection of asynchrony in both the auditory and vibrotactile modalities. Using the method of constant stimuli and a two-alternative forced choice (2AFC), participants were presented with pairs of pure tones played either simultaneously or with various levels of stimulus onset asynchrony (SOA). Target stimuli in both modalities were nested within either: (i) a regularly occurring, predictable rhythm (ii) an irregular, unpredictable rhythm, or (iii) no rhythm at all. Vibrotactile asynchrony detection had higher thresholds and showed greater variability than auditory asynchrony detection in general. Asynchrony detection thresholds for auditory targets but not vibrotactile targets were significantly reduced when the target stimulus was embedded in a regular rhythm as compared to no rhythm. Embedding within an irregular rhythm produced no such improvement. The observed modality asymmetries are interpreted with regard to the superior temporal resolution of the auditory system and specialized brain circuitry supporting auditory–motor coupling. Electronic supplementary material The online version of this article (10.1007/s00221-019-05720-x) contains supplementary material, which is available to authorized users.

Background. Cervical dystonia (CD) is a neurological movement disorder characterized by involuntary contractions of the cervical musculature and is known to be associated with proprioceptive dysfunction in dystonic/nondystonic limbs. Objectives. We examined how neck botulinum neurotoxin (BoNT) injection affects wrist proprioception and the corresponding sensorimotor cortical activity in CD. Method. Wrist position sense acuity of the dominant (right) hand was evaluated in 15 CD and 15 control participants. Acuity measures were a psychophysical position sense discrimination threshold (DT; based on passive joint displacement) and joint position matching error (based on active movement). Cortical activity during the motor preparation period of the active joint position matching was examined using electroencephalography. Results. In their symptomatic state, patients demonstrated a significantly higher wrist proprioceptive DT, indicating an abnormal passive wrist position sense. Yet BoNT injections had no significant effect on this threshold. During active joint position matching, errors were significantly larger in patients, but this difference vanished after the administration of BoNT. Motor preparation of active wrist position matching was associated with a significantly higher rise of β-band (13-30 Hz) power over contralateral somatosensory-motor cortical areas in patients. This excessive cortical activity significantly declined post-BoNT. Conclusion. Wrist proprioceptive perception during passive/active movements is abnormal in CD. An excessive rise of premotor/motor cortical β-oscillations during motor planning is associated with this proprioceptive dysfunction. Neck BoNT injections normalized the cortical processing of proprioceptive information from nonsymptomatic limbs, indicating that local injections may affect the central mechanisms of proprioceptive function in CD.

Background High frequency alternating current (HFAC) stimulation have been shown to produce a peripheral nerve conduction block. Currently, all the studies applying HFAC stimulation in clinical studies, have employed frequencies below 10 kHz. The main aim of this work was to investigate the neuromodulatory effect of transcutaneous 20 kHz stimulation on somatosensory and pain thresholds, and maximal handgrip strength. Methods A randomized, crossover, single-blinded, placebo-controlled trial was conducted following recruitment of fourteen healthy volunteers. Transcutaneous stimulation at 20 kHz and sham stimulation were applied over the ulnar and median nerves of fourteen healthy volunteers for 20 min. Maximal handgrip strength (MHS), mechanical detection threshold (MDT) and pressure pain threshold (PPT) were registered prior to, during (15 min), immediately after the end (20 min), and 10 min following stimulation. Results The 20 kHz stimulation showed a lower MHS during the stimulation at the 15 min (30.1 kgs SE 2.8) and at 20 min (31.8 kgs, SE 2.8) when compared to sham stimulation (35.1 kgs, SE 3.4; p p = 0.03, respectively). The 20 kHz stimulation resulted in a slight increase in MDT at 15 min (0.25 mN; 0.25–2.00) when compared to the sham stimulation (0.25 mN; 0.25–0.25; p = 0.02), and no effects were showed for PPT. Conclusions High-frequency stimulation at 20 kHz suggests a partial block of nerve activity. Studies in subjects with neurological disorders characterized by nerve hyperactivity are needed to confirm the clinical impact of this non-invasive electrical stimulation technique. Trial registration NCT, NCT02837458. Registered on 12 April 2017.

Background. Many Type 2 diabetes (T2DM) patients in Korea take Korean Red Ginseng (KRG) for various reasons. In this study, we investigated the effects of KRG administration on diabetic peripheral neuropathy in T2DM patients. Methods. This study was a randomized, double-blind, placebo-controlled trial. Participants were randomly allocated to either the placebo or KRG group and took corresponding tablets for 24 weeks. The primary outcomes were changes in current perception threshold (CPT) at week 24. Secondary outcomes were altered fasting plasma glucose, HbA1c, and various metabolic and inflammatory markers at week 24. Results. Sixty-one patients completed the study. The CPT of the lower extremities at various frequencies exhibited significant improvements at week 24 in the KRG group. Other metabolic parameters were not altered after 24 weeks in both groups. In the subgroup analysis, CPT levels were improved in those with a longer diabetes duration or who already had neuropathy at the beginning of the study, and insulin resistance was improved in patients with a shorter diabetes duration. Conclusion. Twenty-four week administration of KRG in T2DM patients resulted in a significant improvement in neuropathy, especially in those with a longer diabetes duration. A further, larger population study with a longer follow-up period is warranted to verify the effects of KRG on diabetic neuropathy.

Sensory dysfunction is a common consequence of many forms of neurological injury. Rehabilitative paradigms that incorporate sensory retraining can provide modest benefits, but the majority of patients are left with lasting sensory loss. We have developed a novel strategy that uses closed-loop vagus nerve stimulation (VNS) paired with motor rehabilitation to facilitate recovery after neurological injury. VNS drives robust, phasic activation of neuromodulatory networks concurrent with rehabilitation to enhance synaptic plasticity and support recovery. A clinical case report provides initial evidence that a similar implementation of closed-loop VNS paired with a tactile rehabilitation regimen could improve recovery of somatosensory function. Here, we sought to build on this promising initial clinical data and rigorously evaluate the ability of VNS paired with tactile rehabilitation to improve recovery in an animal model of chronic sensory loss. The study design, including planned sample size, assessments, and statistical comparisons, was preregistered prior to beginning data collection (https://osf.io/xsnj5/). VNS paired with tactile rehabilitation resulted in a significant and nearly complete recovery of mechanosensory withdrawal thresholds. Equivalent tactile rehabilitation without VNS failed to improve sensory function. This VNS-dependent restoration of sensory thresholds was maintained for several months after the cessation of stimulation, illustrating long-term benefits. Moreover, VNS paired with tactile rehabilitation resulted in significant generalized improvements in other measures of forelimb sensorimotor function, including forelimb use asymmetry and paw placement. Given the safety and tolerability of VNS therapy, these findings suggest that incorporating VNS paired with sensory retraining into rehabilitative regimens may represent a fundamentally new method to increase recovery of sensory function after neurological injury.

PURPOSE: To develop location specific models of normal, age-related changes in the macular ganglion cell layer (GCL) from optical coherence tomography (OCT). Using these OCT-derived models, we predicted visual field (VF) sensitivity and compared these results to actual VF sensitivities. DESIGN: Retrospective cohort study METHODS: Single eyes of 254 normal participants were retrospectively enrolled from the Centre for Eye Health (Sydney, Australia). Macular GCL measurements were obtained using Spectralis OCT. Cluster algorithms were performed to identify spatial patterns demonstrating similar age-related change. Quadratic and linear regression models were subsequently utilized to characterize age-related GCL decline. 40 participants underwent additional testing with Humphrey VFs, and 95% prediction intervals were calculated to measure the predictive ability of structure-function models incorporating cluster-based pooling, age-correction and consideration of spatial summation. RESULTS: Quadratic GCL regression models provided a superior fit (p =

Aims Few studies have examined how improved metabolic control might influence vibration perception thresholds (VPTs). The aim of this study was to evaluate if improved HbA1c can influence vibration thresholds in adults with type 1 diabetes (T1DM). Methods VPTs were investigated at six frequencies (4–125 Hz) using VibroSense Meter in the sole of the foot at two occasions in 159 T1DM patients, at the heads of the first and fifth metatarsal bones, i.e. MTH1 and MTH5, respectively. The participants were divided into three groups: group A: HbA1c improved by more than 1 mmol/mol (n = 95), group B: HbA1c deteriorated by more than 1 mmol/mol (n = 48) and group C: HbA1c unchanged (± 1 mmol/mol) (n = 16) compared to baseline. Results In group A, the mean z-score, reflecting the combined effect of all VPTs, improved being lower at the follow-up than at the baseline [0.2 (− 0.3 to 1.2) vs. −0.1 (− 0.7 to 0.8), p = 0.00002]. VPTs improved at 4 and 64 Hz at both MTH1 (metatarsal head 1) and MTH5. The VPTs at 125 Hz frequency improved at MTH5, but not at MTH1. No significant differences were seen in group B or group C. Conclusions Lower HbA1c and lower VPTs in T1DM patients were associated with improved VPT, suggesting a reversible effect on nerve function by improved metabolic control.

IntroductionElevated temporal discrimination thresholds (TDT) have been found in cervical dystonia (CD) and unaffected first-degree relatives, indicating autosomal dominant inheritance with reduced penetrance, serving as an endophenotype and being indicative of abnormal inhibitory processing within the brainstem-basal ganglia circuits. The blink reflex R2 recovery cycle (BRRC) is also a measure of excitability of brainstem-basal ganglia circuits, and inconsistent findings are reported in CD. The aim was to investigate TDT and BRRC in CD and evaluate its reliability as an endophenotype.Methods29 patients with isolated cervical dystonia (mean age: 56.1 ± 14.3, female n = 18) and 29 age- and gender-matched healthy controls (mean age: 56.0 ± 14.2, female n = 18) were evaluated using a TDT-paradigm, performed as previously described by testing visual, tactile and visual-tactile temporal discrimination thresholds, and the BRRC, investigated with electrical and air puff stimulation.ResultsMean visual-tactile (p = 0.001) and visual TDTs (p = 0.015) differed between CD and controls; tactile TDTs revealed no group differences (p = 0.232). No between group differences were found for BRRC using either electrical or air puff stimulation (p = 0.117). There was no correlation between the elevation of TDTs and the degree of BRRC-inhibition in CD.ConclusionOur findings support the hypothesis that the TDT is an endophenotype in CD. BRRC testing did not demonstrate disinhibition of brainstem-basal ganglia circuits in CD. In contrast to TDT, the BRRC seems not to represent an endophenotype in cervical dystonia.

Aims To determine the incidence of olfactory dysfunction in common variable immunodeficiency patients. To evaluate the correlation between olfactory dysfunction and chronic rhinosinusitis in this class of patients. Materials and methods Fifty patients, with a diagnosis of common variable immunodeficiency and under immunoglobulin replacement therapy, were submitted to an otolaryngology physical examination and a CT scan of the craniofacial structures in order to show the presence of signs of chronic rhinosinusitis. An olfactory function evaluation was executed using the Sniffin’ Sticks Test, with assessment of olfactory threshold, discrimination, identification and overall composite scores (TDI: threshold-discrimination-identification score). Results An olfactory dysfunction was found in 23 (46%) common variable immunodeficiency patients, with hyposmia and anosmia respectively present in 65% and 38% of them. The mean TDI score in the study group was 27.7. Common variable immunodeficiency patients with CRS presented a more suggestive increase of the olfactory threshold, discrimination and identification compared to those without chronic rhinosinusitis. Conclusion In conclusion, patients with common variable immunodeficiency seem to suffer from olfactory disorders more than healthy people. One of the causal factors could be considered the presence of rhinosinusal pathologies.

The toxic effects resulting from inhalation exposure depend on both the concentration (C) of the inhaled substance and the exposure duration (t), including the assumptions that the exposure-limiting toxic effect is linearly linked with the accumulated C × t (inhaled dose), and detoxification or compensatory responses diminishing this dose are negligible. This interrelationship applies for both constant and fluctuating concentrations and is usually expressed by the toxic load equation Cn × t = constant effect (k). The toxic load exponent ‘n’ is derived from both C- and t-dependent exponents with Cb2×tb3 = k with n = b2/b3. This model is taken as a fundamental basis for assessing the acute hazard posed by atmospheric releases of noxious substances, whether deliberate or accidental. Despite its universal use, especially for inhaled irritants, the toxicological significance of this mathematical construct is still discussed controversially. With n = 1 this equation is called Haber’s rule. The underlying assumption is that the exposure-based calculated and the actually inhaled Cb2×tb3 are identical. Unlike the calculated dose, the latter is dependent on the test species and its t-dependent change in respiratory minute volume (MV). The retention patterns of inhaled irritant vapors may differ in obligate nasal breathing rodents and oronasally breathing humans as well. Thus, due to the interdependence of n on both C, t and k, this mathematical construct generates a bioassay-specific ‘n’ which can hardly be considered as human-equivalent, especially following exposure to sensory irritants known to elicit reflex-related changes in MV. The C- and t-dependent impact on Cn × t = k was analyzed with the sensory irritant n-butyl monoisocyanate and compared with t-dependent changes elicited by highly, moderately, and poorly water-soluble sensory irritants ammonia, toluene diisocyanate, and phosgene, respectively. This comparison reveals that n depends on several factors: In cases where MV is instantly and plateau-like depressed with onset of exposure, n appears to be most dependent on Cb2 × MV whereas for a similar slower time-dependent response n becomes more dependent on MV × tb3. For any ensuing risk characterization that focuses on acute non-lethal threshold Cb2 × tb3’s, the sensory irritation-related depression in MV must be known to arrive at meaningful conclusions. In summary, both Cn- and t-dependent dosimetry-related pitfalls may occur in acute bioassays on rodents following inhalation exposure to irritants. These must be identified and dealt with judiciously prior to translation to apparently similar human exposures. By default, extrapolations from one duration to another should start with that Cn × t eliciting the least depression in MV with n = 1.

PurposeTo review central structure-function (SF) relationships in glaucoma; to compare contributions of within-session and between-session variability to total variability of macular optical coherence tomography (OCT) thickness measurements; and to test the hypothesis that longitudinal within-eye variability of central SF relationships is smaller than between-individual variability.MethodsWe reviewed the pertinent literature on central SF relationships in glaucoma. Thirty-eight eyes (20 normal or glaucoma subjects) had×3 macular images per session over 3 sessions, and superpixels thickness measurements for ganglion cell layer (GCL), ganglion cell/inner plexiform layer (GCIPL), ganglion cell complex (GCC), and full macular thickness (FMT) were exported. Linear mixed models were used for estimating contributions of between- and within-session variability to total thickness variability. One hundred twenty eyes with ≥3 10° visual fields (VFs)/OCT images were enrolled for the longitudinal study. We investigated within-eye longitudinal SF relationships (GCIPL thickness vs VF total deviations) with a change-point regression model and compared within-eye to between-individual variabilities with components-of-variance models.ResultsIn the cross-sectional study, the between-session component contributed 8%, 11%, 11%, and 36% of total variability for GCL, GCIPL, GCC, and FMT, respectively. In the longitudinal study, between-individual variability explained 78%, 77%, and 67% of total SF variability at 3.4°, 5.6°, and 6.8° eccentricities, respectively (P < .05). SF relationships remained stable over time within individual eyes.ConclusionsWithin-session variability accounts formost of macular thickness variability over time. Longitudinal within-eye SF variability is smaller than between-individual variability. Study of within-eye SF relationships could help clinicians better understand SF linking in glaucoma and help refine progression algorithms. NOTE: Publication of this article is sponsored bythe American Ophthalmological Society.

IntroductionLoss of sensation due to diabetes‐related neuropathy often leads to diabetic foot ulceration. Several test instruments are used to assess sensation, such as static and moving 2‐point discrimination (S2PD, M2PD), monofilaments, and tuning forks.MethodsMokken scale analysis was applied to the Rotterdam Diabetic Foot Study data to select hierarchies of tests to construct measurement scales.ResultsWe developed 39‐item and 31‐item scales to measure loss of sensation for research purposes and a 13‐item scale for clinical practice. All instruments were strongly scalable and reliable. The 39 items can be classified into 5 hierarchically ordered core clusters: S2PD, M2PD, vibration sense, monofilaments, and prior ulcer or amputation.DiscussionGuided by the presented scales, clinicians may better classify the grade of sensory loss in diabetic patients’ feet. Thus, a more personalized approach concerning individual recommendations, intervention strategies, and patient information may be applied.

Definitive diagnostic criteria for small fibre neuropathy have yet to be established, with implications both for clinical practice and for the design of clinical trials. Devigili et al. demonstrate that a combined approach – with clinical, functional and structural assessment of small nerve fibres – improves the reliability of diagnosis., The diagnostic criteria for small fibre neuropathy are not established, influencing the approach to patients in clinical practice, their access to disease-modifying and symptomatic treatments, the use of healthcare resources, and the design of clinical trials. To address these issues, we performed a reappraisal study of 150 patients with sensory neuropathy and a prospective and follow-up validation study of 352 new subjects with suspected sensory neuropathy. Small fibre neuropathy diagnostic criteria were based on deep clinical phenotyping, quantitative sensory testing (QST) and intraepidermal nerve fibre density (IENFD). Small fibre neuropathy was ruled out in 5 of 150 patients (3.3%) of the reappraisal study. Small fibre neuropathy was diagnosed at baseline of the validation study in 149 of 352 patients (42.4%) based on the combination between two clinical signs and abnormal QST and IENFD (69.1%), abnormal QST alone (5.4%), or abnormal IENFD alone (20.1%). Eight patients (5.4%) had abnormal QST and IENFD but no clinical signs. Further, 38 patients complained of sensory symptoms but showed no clinical signs. Of those, 34 (89.4%) had normal QST and IENFD, 4 (10.5%) had abnormal QST and normal IENFD, and none had abnormal IENFD alone. At 18-month follow-up, 19 of them (56%) reported the complete recovery of symptoms and showed normal clinical, QST and IENFD findings. None of those with one single abnormal test (QST or IENFD) developed clinical signs or showed abnormal findings on the other test. Conversely, all eight patients with abnormal QST and IENFD at baseline developed clinical signs at follow-up. The combination of clinical signs and abnormal QST and/or IENFD findings can more reliably lead to the diagnosis of small fibre neuropathy than the combination of abnormal QST and IENFD findings in the absence of clinical signs. Sensory symptoms alone should not be considered a reliable screening feature. Our findings demonstrate that the combined clinical, functional and structural approach to the diagnosis of small fibre neuropathy is reliable and relevant both for clinical practice and clinical trial design.

Aim: This study aimed to evaluate differences in tactile acuity (TA) in people with non-specific persistent low back pain (NSPLBP) with and without predominant central sensitisation (CS).Me...

Objective To provide an evidence-based recommendation for the management of olfactory dysfunction in accordance with the consensus reached by the Subcommittee of the Japanese Clinical Practice Guideline for olfactory dysfunction in the Japanese Rhinologic Society. Methods Seven clinical questions (CQs) regarding the management of olfactory dysfunction were formulated by the subcommittee of the Japanese Clinical Practice Guideline for olfactory dysfunction. We searched the literature published between April 1990 and September 2014 using PubMed, the Cochrane Library, and Ichushi Web databases. The main search terms were “smell disorder,” “olfactory dysfunction,” “olfactory loss,” “olfactory disturbance,” “olfactory impairments,” “olfaction disorder,” “smell disorder,” “anosmia,” “cacosmia,” and “dysosmia.” Based on the results of the literature review and the expert opinion of the Subcommittee, 4 levels of recommendation, from A—strongly recommended to D—not recommended, were adopted for the management of olfactory dysfunction. Results Both oral and locally administered corticosteroids have been strongly recommended for patients with olfactory dysfunction due to chronic rhinosinusitis. Nasal steroid spray and antihistamine drugs have been moderately recommended for patients with allergic rhinitis. Although no drugs have been deemed to be truly effective for post-viral olfactory dysfunction by randomized-controlled trials (RCTs) or placebo-controlled trials, olfactory training using odorants has been reported to be effective for improving olfactory function. There is considerable evidence that olfactory testing is useful for differential diagnosis, prediction of disease progression, and early detection of cognitive decline in neurodegenerative diseases. Conclusion The Clinical Practice Guideline has developed recommendations for the management of various aspects of olfactory dysfunction.

Objective: Haptic perception is critical for prosthetic users to control their prosthetic hand intuitively. In this study, we seek to evaluate the haptic perception evoked from concurrent stimulation trains through multiple channels using transcutaneous nerve stimulation. Methods: A 2 × 8 electrode grid was used to deliver current to the median and ulnar nerves in the upper arm. Different electrodes were first selected to activate the sensory axons, which can elicit sensations at different locations of the hand. Charge-balanced bipolar stimulation was then delivered to two sets of electrodes concurrently with a phase delay (dual stimulation) to determine whether the evoked sensation can be constructed from sensations of single stimulation delivered separately at different locations (single stimulation) along the electrode grid. The temporal delay between the two stimulation trains was altered to evaluate potential interference. The short-term stability of the haptic sensation within a testing session was also evaluated. Results: The evoked sensation during dual stimulation was largely a direct summation of the sensation from single stimulations. The delay between the two stimulation locations had minimal effect on the evoked sensations, which was also stable over repeated testing within a session. Conclusion: Our results indicated that the haptic sensations at different regions of the hand can be constructed by combining the response from multiple stimulation trains directly. The interference between stimulations were minimal. Significance: The outcomes will allow us to construct specific haptic sensation patterns when the prosthesis interacts with different objects, which may help improve user embodiment of the prosthesis.

The cholinergic system is known to strongly modulate perceptual and cognitive processes, and the alpha7 subunit of the cholinergic nicotinic receptor (CHRNA7) is broadly expressed within the visual system. Here, we assessed whether genetic variations of CHRNA7 affect coherent motion perception. Motion perception has been shown to decline with age, and it has previously been suggested that the effects of genetic variations are magnified by age. Therefore, we tested both older (n = 62) and younger adults (n = 63). We found that motion coherence thresholds were significantly higher for older compared to younger adults, which is in accordance with previous studies. Interestingly, there was a strong relationship between variants of the SNP rs2337980 of the CHRNA7 and motion direction discrimination. In particular, participants carrying the TC genotype had considerably lower motion coherence thresholds than CC carriers. The effect of genotype did not interact with age. Our results show that genetic variations are associated with perceptual performance, but are unlikely to explain age-related changes.

Although much research has been devoted to the neural correlates of motion perception, the processing of speed of motion is still a topic of discussion. Apart from patient LM, no in-depth clinical research has been done in the past 20 years on this topic. In the present study, we investigated patient TD, who suffered from the rare disorder akinetopsia due to bilateral lesions of V5 after stroke. By means of a Random-Dot-Kinematogram (RDK) in which speed was varied systematically, it was found that TD was impaired in perceiving the direction of movement at speeds exceeding 9 deg/s. Our study suggests that V5 plays an important role in processing high-speed visual motion and further implies that V5 does not play a crucial role in processing low-speed visual motion. A remarkable finding, which has not been shown before, was that TD always reported the opposite direction of the actual movement at a speed of 24 deg/s. This suggests a form of the continuous wagon wheel illusion, which might have been caused by intact brain areas operating at different sampling rates than area V5.

Amblyopia is associated with a range of well-known visual spatial deficits, which include reduced contrast sensitivity, spatial distortions, interocular suppression, and impaired stereopsis. Previous work has also pointed to deficits in processing dynamic visual information, but it is unknown whether these deficits influence performance under binocular conditions. We examined the effects of temporal modulation on contrast sensitivity and binocular interactions in a preliminary study of 8 adults with amblyopia and 14 normally-sighted control subjects. For each observer, we measured interocular balance and stereopsis thresholds with binocular flicker across a range of four temporal (0, 4, 7.5, and 12 Hz) and spatial (1, 2, 4, and 8 cpd) frequencies. Interocular balance was estimated by varying the relative contrast of dichoptic letter pairs to produce perceptual reports of each letter with equal frequency, and stereopsis thresholds were measured by determining the minimum disparity at which subjects identified a front-depth target with 75% accuracy. Consistent with previous findings, we observed greater interocular imbalance and impaired stereoacuity at high spatial frequencies in amblyopes. In contrast, the effects of temporal frequency on performance were smaller: across both groups, interocular imbalance was largest at mid-to-low temporal frequencies, and stereopsis thresholds were unaffected by temporal frequency. Our results suggest that there may be a previously unreported effect of temporal frequency on interocular balance, as well as a possible dissociation between the effects of flicker on interocular balance and stereopsis.