Maria Feldmann

Epidemiology of benign paroxysmal positional vertigo: a population based study

Objectives: To examine the prevalence and incidence, clinical presentation, societal impact and comorbid conditions of benign paroxysmal positional vertigo (BPPV) in the general population. Methods: Cross-sectional, nationally representative neurotological survey of the general adult population in Germany with a two stage sampling design: screening of 4869 participants from the German National Telephone Health Interview Survey 2003 (response rate 52%) for moderate or severe dizziness or vertigo, followed by validated neurotological interviews (n = 1003; response rate 87%). Diagnostic criteria for BPPV were at least five attacks of vestibular vertigo lasting <1 min without concomitant neurological symptoms and invariably provoked by typical changes in head position. In a concurrent validation study (n = 61) conducted in two specialised dizziness clinics, BPPV was detected by our telephone interview with a specificity of 92% and a sensitivity of 88% (positive predictive value 88%, negative predictive value 92%). Results: BPPV accounted for 8% of individuals with moderate or severe dizziness/vertigo. The lifetime prevalence of BPPV was 2.4%, the 1 year prevalence was 1.6% and the 1 year incidence was 0.6%. The median duration of an episode was 2 weeks. In 86% of affected individuals, BPPV led to medical consultation, interruption of daily activities or sick leave. In total, only 8% of affected participants received effective treatment. On multivariate analysis, age, migraine, hypertension, hyperlipidaemia and stroke were independently associated with BPPV. Conclusion: BPPV is a common vestibular disorder leading to significant morbidity, psychosocial impact and medical costs.

Epidemiology of vestibular vertigo A neurotologic survey of the general population

Objective: The purpose of this study was to determine the prevalence and incidence of vestibular vertigo in the general population and to describe its clinical characteristics and associated factors. Methods: The neurotologic survey had a two-stage general population sampling design: nationwide modified random digit dialing sampling for participation in the German National Telephone Health Interview Survey 2003 (response rate 52%) with screening of a random sample of 4,869 participants for moderate or severe dizziness or vertigo, followed by detailed neurotologic interviews developed through piloting and validation (n = 1,003, response rate 87%). Diagnostic criteria for vestibular vertigo were rotational vertigo, positional vertigo, or recurrent dizziness with nausea and oscillopsia or imbalance. Vestibular vertigo was detected by our interview with a specificity of 94% and a sensitivity of 88% in a concurrent validation study using neurotology clinic diagnoses as an accepted standard (n = 61). Results: The lifetime prevalence of vestibular vertigo was 7.8%, the 1-year prevalence was 5.2%, and the incidence was 1.5%. In 80% of affected individuals, vertigo resulted in a medical consultation, interruption of daily activities, or sick leave. Female sex, age, lower educational level, and various comorbid conditions, including tinnitus, depression, and several cardiovascular diseases and risk factors, were associated with vestibular vertigo in the past year in univariate analysis. In multivariable analysis, only female sex, self-reported depression, tinnitus, hypertension, and dyslipidemia had an independent effect on vestibular vertigo. Conclusions: Vestibular vertigo is common in the general population, affecting more than 5% of adults in 1 year. The frequency and health care impact of vestibular symptoms at the population level have been underestimated.

Burden of Dizziness and Vertigo in the Community

BACKGROUND Dizziness and vertigo are common, however, the cause often remains unexplained. The percentage of vertigo of vestibular origin in individuals with unselected dizziness has not been well examined, and its underestimation may lead to diagnostic bias in primary care. The purpose of this study was to reassess the burden of dizziness in the community and to quantify the contribution of vertigo of vestibular origin. METHODS A nationally representative sample of 4869 adults living in Germany was screened for moderate or severe dizziness, and 1003 individuals with dizziness underwent validated neurotologic interviews to differentiate vestibular vertigo from nonvestibular dizziness according to explicit diagnostic criteria. RESULTS Dizziness/vertigo had a prevalence of 22.9% in the last 12 months and an incidence (first episode of dizziness/vertigo) of 3.1%. For vestibular vertigo, the prevalence was 4.9% [corrected] and the incidence was 1.4%. We also found that 1.8% of unselected adults consulted a physician in the last 12 months for [corrected] dizziness/vertigo (0.9% for vestibular vertigo). Compared with nonvestibular dizziness, vestibular vertigo was more frequently followed by medical consultation (70% vs 54%; P < .001), sick leave (41% vs 15%; P < .001), interruption of daily activities (40% vs 12%; P < .001), and avoidance of leaving the house (19% vs 10%; P = .001). However, more than half of the participants with vestibular vertigo reported nonvestibular diagnoses. Age- and sex-adjusted health-related quality of life was lower in individuals with dizziness and vertigo compared with dizziness-free control subjects. CONCLUSIONS The occurrence of dizziness and vertigo is frequent and associated with a considerable personal and health care burden. Vestibular vertigo accounts for a considerable percentage of this burden, which suggests that diagnosis and treatment of frequent vestibular conditions are important issues in primary care.

Migrainous vertigo Prevalence and impact on quality of life

Objective: To investigate the epidemiology of migrainous vertigo (MV) in the general population by assessing prevalence, clinical features, comorbid conditions, quality of life, and health care utilization. Methods: We screened a representative sample of the adult population in Germany (n = 4,869) for moderate or severe dizziness/vertigo and followed up with validated neurotologic telephone interviews (n = 1,003). Diagnostic criteria for MV were as follows: 1) recurrent vestibular vertigo; 2) migraine according to the International Headache Society; 3) migrainous symptoms during at least two vertiginous attacks (migrainous headache, photophobia, phonophobia, or aura symptoms); and 4) vertigo not attributed to another disorder. In a concurrent validation study (n = 61) the interviews had a sensitivity of 84% and a specificity of 94% for vestibular vertigo and 81% and 100% for migraine. Results: The lifetime prevalence of MV was 0.98% (95% CI 0.70 to 1.37), the 12-month prevalence 0.89% (95% CI 0.62 to 1.27). Spontaneous rotational vertigo was reported by 67% of participants with MV while 24% had positional vertigo. Twenty-four percent always experienced headaches with their vertigo. Logistic regression analysis comparing participants with MV with dizziness-free migraineurs showed an independent association with coronary heart disease but not with sex, age, migrainous aura, education, stroke, hypertension, hyperlipidemia, body mass index, or depression. Age-adjusted health-related quality of life scores (SF-8 Health Survey) were consistently lower in participants with MV compared to dizziness-free controls. Two thirds of participants with MV had consulted a doctor but only 20% of these were diagnosed with MV. Conclusions: Migrainous vertigo is relatively common but underdiagnosed in the general population and has considerable personal and healthcare impact.

Bias in iterative reconstruction of low-statistics PET data: benefits of a resolution model.

Ordered-subset expectation maximization (OSEM) is a widely used method of reconstructing PET data. Several authors have reported bias when reconstructing frames containing few counts via OSEM, although the level of bias reported varies substantially. Such bias may lead to errors in biological parameters as derived via dynamic PET. We examine low-statistics bias in OSEM reconstruction of patient data and estimate the subsequent errors in biological parameter estimates. Patient listmode data were acquired during a [11C]-DASB scan using a brain PET scanner, the high resolution research tomograph (HRRT). These data were sub-sampled to create many independent, low-count replicates. Each replicate was reconstructed with and without the use of an image based resolution model (PSF), from which bias and variance were calculated as a function of the noise equivalent counts (NEC). Time-activity curves were subsequently generated by Monte Carlo simulation and used to study the propagation of bias from the images into the biological parameters of interest, for which noise and bias were based on the NEC. The investigation was complemented by simulation of a PET scanner. Significant bias was observed when reconstructing data of low statistical quality, for both human and simulated data. For human data, this bias was substantially reduced by including a PSF model (e.g. caudate head, 1.7 M NEC, -5.5 % bias with PSF, -13 % bias without PSF). For the observed levels of bias, Monte Carlo simulations predicted biases in the binding potential of -4 and -10 % (with/without PSF). The use of the PSF changed the variance characteristics of the images, reducing variance at the voxel level for low to moderate numbers of iterations. We conclude that OSEM reconstruction of dynamic PET data can yield parameter estimates of acceptable accuracy (for DASB), despite producing biased images at low statistics. This is however dependent upon the application. The use of a resolution model is shown to reduce bias and is thus recommended. The most likely mechanism for this reduction is the suppression of noise. The magnitude of the bias for other tracers and methods of data analysis is yet to be evaluated.

Pre- and Postsynaptic Serotonergic Differences in Males with Extreme Levels of Impulsive Aggression Without Callous Unemotional Traits: A Positron Emission Tomography Study Using 11C-DASB and 11C-MDL100907

BACKGROUND Impulsive aggression (IA) in adults is associated with brain serotonin (5-HT) system abnormalities and is more common following childhood adversity. Within aggressive behavior, IA and callous unemotional (CU) traits are core components of differentiable factors with opposing 5-HT abnormalities. We aimed to investigate 5-HT abnormalities in IA and potential correlations with severity of childhood adversity while controlling for confounding 5-HT effects of high CU traits and mental disorders. METHODS Healthy male subjects (mean age 34 ± 9 years) without high CU traits were recruited with IA ratings in the high (n = 14) and low (n = 13) population extremes. Serotonin transporter (SERT) and 5-HT(2A) receptor availability was measured in multiple brain regions using positron emission tomography with (11)C-DASB and (11)C-MDL100907, respectively, and compared between high-IA and low-IA groups. Correlations were measured between SERT and 5-HT(2A) receptor availability, impulsivity and aggression, and childhood adversity. RESULTS Compared with the low-IA group, SERT were significantly higher in brainstem regions in the high-IA group (by 29.0% ± 11.4%) and modestly lower across cortical regions (by 11.1% ± 6.0%), whereas 5-HT(2A) receptors were also modestly lower (by 8.6% ± 4.0%). Across all subjects, brainstem SERT were significantly positively correlated with impulsivity, aggression, and childhood trauma ratings. Within the high-IA group, higher brainstem SERT was most strongly predicted by severity of childhood trauma (r = .76 in midbrain). CONCLUSIONS Pre-and postsynaptic 5-HT differences are present in men with high levels of IA and are strongly suggestive of a persisting effect of childhood adversity on serotonergic neurodevelopment and emotional-behavioral control.

P-glycoprotein imaging in temporal lobe epilepsy: In vivo PET experiments with the Pgp substrate [11C]-verapamil

Overexpression of the multidrug efflux transporter P‐glycoprotein (Pgp) at the blood–brain barrier (BBB) is thought to be involved in pharmacoresistance in epilepsy by extruding antiepileptic drugs (AEDs) from their target site. To explore this hypothesis, positron emission tomography (PET) scans were performed with the Pgp substrate–verapamil (VPM) in animal models before and after status epilepticus (SE) and in patients with temporal lobe epilepsy (TLE) and healthy controls. In addition to baseline scans, a second VPM‐PET scan was performed after administration of the Pgp inhibitor tariquidar (TQD), showing that VPM uptake at baseline and its increase after Pgp inhibition are reduced in animals following SE compared to baseline, and in refractory TLE relative to healthy controls. In animal models, brain regions with increased Pgp expression (cerebellum, thalamus, and hippocampus) showed reduced influx rate constants from blood to brain, K1, of the radiolabeled Pgp substrate relative to control animals. In human studies, preliminary findings are lower K1 values in refractory compared to seizure‐free patients and attenuated increase of K1 for temporal lobe regions in patients with TLE compared to healthy controls. In summary, there is lower brain uptake of the Pgp substrate VPM in Pgp‐rich areas of animals 2 days following SE, as well as lower increase in VPM brain uptake after TQD in patients with refractory TLE compared to healthy controls, supporting the hypothesis of increased cerebral Pgp function following prolonged seizures and as a mechanism contributing to drug resistance in refractory epilepsy. The observation of reduced VPM uptake in refractory compared to seizure‐free patients with TLE is consistent with multiple mechanisms affecting Pgp function, including uncontrolled seizures.

Investigation of motion induced errors in scatter correction for the HRRT brain scanner

Patient motion during PET scans introduces errors in the attenuation correction and image blurring leading to false changes in regional radioactivity concentrations. However, the potential effect that motion has on simulation-based scatter correction is not fully appreciated. Specifically for tracers with high uptake close to the edge of head (e.g. scalp and nose) as observed with [11C]Verapamil, mismatches between transmission and emission data can lead to significant quantification errors and image artefacts due to over scatter correction. These errors are linked with unusually high values in the scatter scaling factors (SSF) returned during the single scatter simulation process implemented in the HRRT image reconstruction. Reconstruction of μ-map with TXTV (an alternative μ-map reconstruction using non-linear filtering rather than brain segmentation and scatter correction of the transmission data) was found to improve the scatter simulation results for [11C]Verapamil and [18F]FDG. The errors from patient motion were characterised and quantified through simulations by applying realistic transformations to the attenuation map (μ-map). This generated inconsistencies between the emission and transmission data, and introduced large over-corrections of scatter similar to some cases observed with [11C]Verapamil. Automated Image Registration (AIR) based motion correction was also implemented, and found to remove the artifact and recover quantification in dynamic studies after aligning all the PET images to a common reference space.

Epilepsy causing pupillary hippus: an unusual semiology

Altered pupillary behavior is commonly present during and following epileptic seizures, but symptomatic pupillary hippus as the main feature of a seizure has not been reported in the modern literature. We present the case of a woman with epileptic seizures consisting of sustained fluctuation of perception of brightness. Bilateral pupillary hippus is the main semiologic feature.This autonomic phenomenon is selective for the pupils and does not involve other autonomic‐mediated responses. An ictal video illustrates this phenomenon. The epileptogenic region, determined by ictal scalp and intracranial electroencephalography (EEG), is localized in the right posterior parietooccipital areas. Pupillary reflexes can be overridden by cortical input; here authors review the literature and discus the physiologic mechanisms underlying this autonomic phenomenon. Fluctuation in perceptual brightness during epileptic seizures may have a basis in ictal pupillary hippus.

Optimization of methods for quantification of rCBF using high-resolution [15O]H2O PET images

This study aimed to derive accurate estimates of regional cerebral blood flow (rCBF) from noisy dynamic [¹⁵O]H₂O PET images acquired on the high-resolution research tomograph, while retaining as much as possible the high spatial resolution of this brain scanner (2-3 mm) in parametric maps of rCBF. The PET autoradiographic method and generalized linear least-squares (GLLS), with fixed or extended to include spatially variable estimates of the dispersion of the measured input function, were compared to nonlinear least-squares (NLLS) for rCBF estimation. Six healthy volunteers underwent two [¹⁵O]H₂O PET scans with continuous arterial blood sampling. rCBF estimates were obtained from three image reconstruction methods (one analytic and two iterative, of which one includes a resolution model) to which a range of post-reconstruction filters (3D Gaussian: 2, 4 and 6 mm FWHM) were applied. The optimal injected activity was estimated to be around 11 MBq kg⁻¹ (800 MBq) by extrapolation of patient-specific noise equivalent count rates. Whole-brain rCBF values were found to be relatively insensitive to the method of reconstruction and rCBF quantification. The grey and white matter rCBF for analytic reconstruction and NLLS were 0.44 ± 0.03 and 0.15 ± 0.03 mL min⁻¹ cm⁻³, respectively, in agreement with literature values. Similar values were obtained from the other methods. For generation of parametric images using GLLS or the autoradiographic method, a filter of ≥ 4 mm was required in order to suppress noise in the PET images which otherwise produced large biases in the rCBF estimates.