Downregulation of early visual cortex excitability mediates oscillopsia suppression

© 2017 The Authors. Published by American Academy of Neurology. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1212/WNL.0000000000004360Objective: To identify in an observational study the neurophysiologic mechanisms that mediate adaptation to oscillopsia in patients with bilateral vestibular failure (BVF). Methods: We directly probe the hypothesis that adaptive changes that mediate oscillopsia suppression implicate the early visual-cortex (V1/V2). Accordingly, we investigated V1/V2 excitability using transcranial magnetic stimulation (TMS) in 12 avestibular patients and 12 healthy controls. Specifically, we assessed TMS-induced phosphene thresholds at baseline and cortical excitability changes while performing a visual motion adaptation paradigm during the following conditions: baseline measures (i.e., static), during visual motion (i.e., motion before adaptation), and during visual motion after 5 minutes of unidirectional visual motion adaptation (i.e., motion adapted). Results: Patients had significantly higher baseline phosphene thresholds, reflecting an underlying adaptive mechanism. Individual thresholds were correlated with oscillopsia symptom load. During the visual motion adaptation condition, no differences in excitability at baseline were observed, but during both the motion before adaptation and motion adapted conditions, we observed significantly attenuated cortical excitability in patients. Again, this attenuation in excitability was stronger in less symptomatic patients. Conclusions: Our findings provide neurophysiologic evidence that cortically mediated adaptive mechanisms in V1/V2 play a critical role in suppressing oscillopsia in patients with BVF

Diabetic Dead-in-Bed Syndrome: A Possible Link to a Cardiac Ion Channelopathy

Sudden unexpected nocturnal death among patients with diabetes occurs approximately ten times more commonly than in the general population. Malignant ventricular arrhythmia due to Brugada syndrome has been postulated as a cause, since a glucose-insulin bolus can unmask the Brugada electrocardiographic signature in genetically predisposed individuals. In this report we present a 16-year-old male with insulin-dependent diabetes who died suddenly at night. His diabetes had been well controlled, without significant hypoglycaemia. At autopsy, he had a full stomach and a glucose level of 7 mmol/L in vitreous humor, excluding hypoglycaemia. Genetic analysis of autopsy DNA revealed a missense mutation, c.370A>G (p.Ile124Val), in the GPD1L gene. A parent carried the same mutation and has QT prolongation. Mutations in this gene have been linked to Brugada syndrome and sudden infant death. The patient may have died from a ventricular arrhythmia, secondary to occult Brugada syndrome, triggered by a full stomach and insulin. The data suggest that molecular autopsies are warranted to investigate other cases of the diabetic dead-in-bed syndrome

Vestibular Perception following Acute Unilateral Vestibular Lesions.

Little is known about the vestibulo-perceptual (VP) system, particularly after a unilateral vestibular lesion. We investigated vestibulo-ocular (VO) and VP function in 25 patients with vestibular neuritis (VN) acutely (2 days after onset) and after compensation (recovery phase, 10 weeks). Since the effect of VN on reflex and perceptual function may differ at threshold and supra-threshold acceleration levels, we used two stimulus intensities, acceleration steps of 0.5°/s(2) and velocity steps of 90°/s (acceleration 180°/s(2)). We hypothesised that the vestibular lesion or the compensatory processes could dissociate VO and VP function, particularly if the acute vertiginous sensation interferes with the perceptual tasks. Both in acute and recovery phases, VO and VP thresholds increased, particularly during ipsilesional rotations. In signal detection theory this indicates that signals from the healthy and affected side are still fused, but result in asymmetric thresholds due to a lesion-induced bias. The normal pattern whereby VP thresholds are higher than VO thresholds was preserved, indicating that any 'perceptual noise' added by the vertigo does not disrupt the cognitive decision-making processes inherent to the perceptual task. Overall, the parallel findings in VO and VP thresholds imply little or no additional cortical processing and suggest that vestibular thresholds essentially reflect the sensitivity of the fused peripheral receptors. In contrast, a significant VO-VP dissociation for supra-threshold stimuli was found. Acutely, time constants and duration of the VO and VP responses were reduced - asymmetrically for VO, as expected, but surprisingly symmetrical for perception. At recovery, VP responses normalised but VO responses remained shortened and asymmetric. Thus, unlike threshold data, supra-threshold responses show considerable VO-VP dissociation indicative of additional, higher-order processing of vestibular signals. We provide evidence of perceptual processes (ultimately cortical) participating in vestibular compensation, suppressing asymmetry acutely in unilateral vestibular lesions

Head-Jolting Nystagmus Occlusion of the Horizontal Semicircular Canal Induced by Vigorous Head Shaking

Importance: We report a new syndrome, which we are calling head-jolting nystagmus, that expands the differential diagnosis of head movement–induced paroxysmal vertigo. Observations: Two male patients (65 and 58 years old) described rotational vertigo after violent and brief (1- to 2-second) oscillations of the head (head jolting) that triggered intense horizontal nystagmus lasting 45 seconds. Accelerations of the head required to induce these episodes could only be achieved by the patients themselves. In case 1, the episodes gradually disappeared over a 6-year period. In case 2, magnetic resonance imaging (3-T) suggested a filling defect within the left horizontal semicircular canal. He underwent surgical canal plugging in March 2013 that resolved the symptoms. Conclusions and Relevance: We attribute head-jolting nystagmus to dislodged material within the horizontal semicircular canal and provide a mechanistic model to explain its origin

Ethnic differences in 25-year risk of incident chronic kidney disease among people with type 2 diabetes in New Zealand.

INTRODUCTION: Insights into ethnic differences in the natural history of chronic kidney disease (CKD) among people with type 2 diabetes mellitus (T2DM) might inform clinical strategies to address disparities in hospitalization and mortality. Risks of CKD II-V stages over a 25-year period between New Zealand Europeans (NZEs), Māori and Pasifika, and with T2DM in Auckland, New Zealand (NZ) were compared. RESEARCH DESIGN AND METHODS: As a primary care audit program in Auckland, the Diabetes Care Support Service was linked with national registration databases. People with existing CKD II-V were ruled out. To balance potential confounders, we applied a tapered matching method . 'Quasi-trial'-matched cohorts were set up separately between Māori and NZE and between Pasifika and NZE. Ethnic population differences in risk of any and each stage of CKD over 1994-2018 were examined by weighted Cox regression model. RESULTS: The HRs for developing any CKD, CKD stages II-V for Māori (n=2215) versus NZE (n=2028) were 1.18 (95% CI 0.99 to 1.41), 1.10 (95% CI 0.91 to 1.32), 1.70 (95% CI 1.19 to 2.43), 3.93 (95% CI 2.16 to 7.14), and 3.74 (95% CI 1.74 to 8.05), respectively. Compared with NZE (n=2474), the HRs for developing any CKD, CKD stages II-V for Pasifika (n=3101) were 1.31 (95% CI 1.09 to 1.57), 1.26 (95% CI 1.05 to 1.52), 1.71 (95% CI 1.14 to 2.57), 3.75 (95% CI 1.40 to 10.05), and 4.96 (95% CI 1.56 to 15.75), respectively. CONCLUSIONS: Among people with T2DM in NZ, significant ethnic differences exist in the risk of progressing to each stage of CKD (stage V in particular). Mechanism studies underlying these differences, as well as the need for identification of biomarkers to predict the early onset renal lesion, are warranted

Fasting Indicators of Insulin Sensitivity: Effects of Ethnicity and Pubertal Status

OBJECTIVE—To examine the relationship of fasting indicators of insulin sensitivity with a more invasive measure of insulin sensitivity (frequently sampled intravenous glucose tolerance test [FSIVGTT]) and the effect of Tanner stage and ethnicity on that relationship. RESEARCHDESIGNANDMETHODS—Data were analyzed from 149 overweight girls (97 Hispanic and 52 African American) who were either in the early stages of maturation defined by Tanner stages 1 or 2 (52Hispanic and 18 African American) or in the later stages of maturation defined by Tanner stages 4 and 5 (45 Hispanic and 34 African American). Fasting indicators of insulin sensitivity (IS) included fasting insulin and glucose and the homeostasis model assess-ment of insulin resistance (HOMA-IR). IS was derived from an FSIVGTTwithminimalmodeling. RESULTS—In Tanner stages 1 and 2, all fasting indicators were significantly associatedwith IS

Visual Dependency and Dizziness after Vestibular Neuritis

Symptomatic recovery after acute vestibular neuritis (VN) is variable, with around 50% of patients reporting long term vestibular symptoms; hence, it is essential to identify factors related to poor clinical outcome. Here we investigated whether excessive reliance on visual input for spatial orientation (visual dependence) was associated with long term vestibular symptoms following acute VN. Twenty-eight patients with VN and 25 normal control subjects were included. Patients were enrolled at least 6 months after acute illness. Recovery status was not a criterion for study entry, allowing recruitment of patients with a full range of persistent symptoms. We measured visual dependence with a laptop-based Rod-and-Disk Test and severity of symptoms with the Dizziness Handicap Inventory (DHI). The third of patients showing the worst clinical outcomes (mean DHI score 36–80) had significantly greater visual dependence than normal subjects (6.35° error vs. 3.39° respectively, p = 0.03). Asymptomatic patients and those with minor residual symptoms did not differ from controls. Visual dependence was associated with high levels of persistent vestibular symptoms after acute VN. Over-reliance on visual information for spatial orientation is one characteristic of poorly recovered vestibular neuritis patients. The finding may be clinically useful given that visual dependence may be modified through rehabilitation desensitization techniques

Ethnic Differences in Cancer Rates Among Adults With Type 2 Diabetes in New Zealand From 1994 to 2018

Importance People with type 2 diabetes have greater risk for some site-specific cancers, and risks of cancers differ among racial and ethnic groups in the general population of Aotearoa New Zealand. The extent of ethnic disparities in cancer risks among people with type 2 diabetes in New Zealand is unclear. Objective To compare the risks of 21 common adult cancers among Māori, Pasifika, and New Zealand European individuals with type 2 diabetes in New Zealand from 1994 to 2018. Design, Setting, and Participants This population-based, matched cohort study used data from the primary care audit program in Auckland, New Zealand, linked with national cancer, death, and hospitalization registration databases, collected from January 1, 1994, to July 31, 2018, with follow-up data obtained through December 31, 2019. Using a tapered matching method to balance potential confounders (sociodemographic characteristics, lifestyle, anthropometric and clinical measurements, treatments [antidiabetes, antihypertensive, lipid-lowering, and anticoagulant], period effects, and recorded duration of diabetes), comparative cohorts were formed between New Zealand European and Māori and New Zealand European and Pasifika individuals aged 18 years or older with type 2 diabetes. Sex-specific matched cohorts were formed for sex-specific cancers. Exposures Māori, Pasifika, and New Zealand European (reference group) ethnicity. Main Outcomes and Measures The incidence rates of 21 common cancers recorded in nationally linked databases between 1994 and 2018 were the main outcomes. Weighted Cox proportional hazards regression was used to assess ethnic differences in risk of each cancer. Results A total of 33 524 adults were included: 15 469 New Zealand European (mean [SD] age, 61.6 [13.2] years; 8522 [55.1%] male), 6656 Māori (mean [SD] age, 51.2 [12.4] years; 3345 [50.3%] female), and 11 399 Pasifika (mean [SD] age, 52.8 [12.7] years; 5994 [52.6%] female) individuals. In the matched New Zealand European and Māori cohort (New Zealand European: 8361 individuals; mean [SD] age, 58.9 [12.9] years; 4595 [55.0%] male; Māori: 5039 individuals; mean [SD] age, 51.4 [12.3] years; 2542 [50.5%] male), significant differences between New Zealand European and Māori individuals were identified in the risk for 7 cancers. Compared with New Zealand European individuals, the hazard ratios (HRs) among Māori individuals were 15.36 (95% CI, 4.50-52.34) for thyroid cancer, 7.94 (95% CI, 1.57-40.24) for gallbladder cancer, 4.81 (95% CI, 1.08-21.42) for cervical cancer (females only), 1.97 (95% CI, 1.30-2.99) for lung cancer, 1.81 (95% CI, 1.08-3.03) for liver cancer, 0.56 (95% CI, 0.35-0.90) for colon cancer, and 0.11 (95% CI, 0.04-0.27) for malignant melanoma. In the matched New Zealand European and Pasifika cohort (New Zealand European: 9340 individuals; mean [SD] age, 60.6 [13.1] years; 4885 [52.3%] male; Pasifika: 8828 individuals; mean [SD] age, 53.1 [12.6] years; 4612 [52.2%] female), significant differences between New Zealand European and Pasifika individuals were identified for 6 cancers. Compared with New Zealand European individuals, HRs among Pasifika individuals were 25.10 (95% CI, 3.14-200.63) for gallbladder cancer, 4.47 (95% CI, 1.25-16.03) for thyroid cancer, 0.48 (95% CI, 0.30-0.78) for colon cancer, 0.21 (95% CI, 0.09-0.48) for rectal cancer, 0.21 (95% CI, 0.07-0.65) for malignant melanoma, and 0.01 (95% CI, 0.01-0.10) for bladder cancer. Conclusions and Relevance In this cohort study, differences in the risk of 21 common cancers were found between New Zealand European, Māori, and Pasifika groups of adults with type 2 diabetes in New Zealand from 1994 to 2018. Research into the mechanisms underlying these differences as well as additional screening strategies (eg, for thyroid and gallbladder cancers) appear to be warranted