Visual snow syndrome after start of citalopram-novel insights into underlying pathophysiology

Purpose!#!Chronic pain is common in the older population and a significant public health concern. However, comprehensive studies on analgesics use in this age group from Germany are scarce. This study aims to give a comprehensive overview on the use of the most common therapeutic groups of analgesics in community-dwelling older adults from Germany.!##!Methods!#!A cross-sectional study was carried out using data from a German cohort of 2038 community-dwelling adults aged 63-89 years. Descriptive statistics and logistic regression models were applied to assess the utilization of analgesics by age, sex, pain severity, pain duration, and locations.!##!Results!#!One out of four study participants was suffering from high-intensity or disabling pain. Approximately half of those taking analgesics still reported to suffer from high-intensity or disabling pain. Among analgesics users, occasional non-steroidal anti-inflammatory drugs (NSAIDs) use was the most frequent pain therapy (in 43.6% of users), followed by metamizole (dipyrone) use (16.1%), regular NSAIDs use (12.9%), strong opioids use (12.7%), and weak opioids use (12.0%). In multivariate logistic regression models, higher age, higher pain severity, longer pain duration, abdominal pain, and back pain were statistically significantly associated with opioids use. Metamizole use was also statistically significantly associated with higher pain severity but inversely associated with pain duration.!##!Conclusions!#!A significant number of older German adults are affected by high-intensity and disabling chronic pain despite receiving analgesics. Long-term studies are needed to compare the effectiveness and safety of different treatments for chronic pain in older adults

Reflexive and Intentional Saccadic Eye Movements in Migraineurs

Background: Migraine has been postulated to lead to structural and functional changes of different cortical and subcortical areas, including the frontal lobe, the brainstem, and cerebellum. The (sub-)clinical impact of these changes is a matter of debate. The spectrum of possible clinical differences include domains such as cognition but also coordination. The present study investigated the oculomotor performance of patients with migraine with and without aura compared to control subjects without migraine in reflexive saccades, but also in intentional saccades, which involve cerebellar as well as cortical networks. Methods: In 18 patients with migraine with aura and 21 patients with migraine without aura saccadic eye movements were recorded in two reflexive (gap, overlap) and two intentional (anti, memory) paradigms and compared to 25 controls without migraine. Results: The main finding of the study was an increase of saccade latency in patients with and without aura compared to the control group solely in the anti-task. No deficits were found in the execution of reflexive saccades. Conclusions: Our results suggest a specific deficit in the generation of correct anti-saccades, such as vector inversion. Such processes are considered to need cortical networks to be executed correctly. The parietal cortex has been suggested to be involved in vector inversion processes but is not commonly described to be altered in migraine patients. It could be discussed that the cerebellum, which is recently thought to be involved in the pathophysiology of migraine, might be involved in distinct processes such as spatial re-mapping through known interconnections with parietal and frontal cortical areas

Age- and frequency-dependent changes in dynamic contrast perception in visual snow syndrome

OBJECTIVE Patients with visual snow syndrome (VSS) suffer from a debilitating continuous (\textquotedblTV noise-like\textquotedbl) visual disturbance. They report problems with vision at night and palinopsia despite normal visual acuity. The underlying pathophysiology of VSS is largely unknown. Currently, it is a clinical diagnosis based on the patient's history, an objective test is not available. Here, we tested the hypothesis that patients with VSS have an increased threshold for detecting visual contrasts at particular temporal frequencies by measuring dynamic contrast detection-thresholds. METHODS Twenty patients with VSS were compared to age-, gender-, migraine- and aura-matched controls in this case-control study. Subjects were shown bars randomly tilted to the left or right, flickering at six different frequencies (15 Hz, 20 Hz, 25 Hz, 30 Hz, 35 Hz, 40 Hz). The contrast threshold (CT) for detection of left or right tilt was measured in a two-alternative adaptive forced-choice procedure (QUEST). The threshold was defined as the Michelson contrast necessary to achieve the correct response in 75% of the cases. RESULTS The CT increased for higher flicker frequencies (ANOVA: main effect frequency: F (5,180) = 942; p < 0.001), with an additional significant frequency*diagnosis interaction (ANOVA: F (5,180) = 5.00; p < 0.001). This interaction effect was due to an increased CT at a flicker frequency of 15 Hz in the VSS cohort (VSS: MC = 1.17%; controls: MC = 0.77%). At the other frequencies, group comparisons revealed no differences. Furthermore, in the VSS cohort we observed an increase of CT with higher age (r = 0.69; p < 0.001), which was not seen in controls (r = 0.30; p = 0.20). CONCLUSIONS This study demonstrates a lower visual contrast sensitivity exclusively at 15 Hz in VSS patients and demonstrates frequency-dependent differences in dynamic contrast vision. The peak sensitivities of both parvo- and magnocellular visual pathways are close to a frequency of about 10 Hz. Therefore, this frequency seems to be of crucial importance in everyday life. Thus, it seems plausible that the impairment of contrast sensitivity at 15 Hz might be an important pathophysiological correlate of VSS. Furthermore, the overall age-related decrease in contrast sensitivity only in VSS patients underscores the vulnerability of dynamic contrast detection in VSS patients. Dynamic CT detection seems to be a promising neurophysiological test that may contribute to the diagnosis of VSS

Integrated multilayer stretchable printed circuitboards paving the way for deformable active matrix

Conventional rigid electronic systems use a number of metallization layers to route all necessary connections to and from isolated surface mount devices using well-established printed circuit board technology. In contrast, present solutions to prepare stretchable electronic systems are typically confined to a single stretchable metallization layer. Crossovers and vertical interconnect accesses remain challenging; consequently, no reliable stretchable printed circuit board (SPCB) method has established. This article reports an industry compatible SPCB manufacturing method that enables multilayer crossovers and vertical interconnect accesses to interconnect isolated devices within an elastomeric matrix. As a demonstration, a stretchable (260%) active matrix with integrated electronic and optoelectronic surface mount devices is shown that can deform reversibly into various 3D shapes including hemispherical, conical or pyramid

Gait analysis in PSP and NPH Dual-task conditions make the difference

Objective To test whether quantitative gait analysis of gait under single- and dual-task conditions can be used for a differential diagnosis of progressive supranuclear palsy (PSP) and idiopathic normalpressure hydrocephalus (iNPH). Methods In this cross-sectional study, temporal and spatial gait parameters were analyzed in 38 patients with PSP (Neurological Disorders and Stroke and Society for Progressive Supranuclear Palsy diagnostic criteria), 27 patients with iNPH (international iNPH guidelines), and 38 healthy controls. A pressure-sensitive carpet was used to examine gait under 5 conditions: single task (preferred, slow, and maximal speed), cognitive dual task (walking with serial 7 subtractions), and motor dual task (walking while carrying a tray). Results The main results were as follows. First, both patients with PSP and those with iNPH exhibited significant gait dysfunction, which was worse in patients with iNPH with a more broad-based gait (p < 0.001). Second, stride time variability was increased in both patient groups, more pronounced in PSP (p = 0.009). Third, cognitive dual task led to a greater reduction of gait velocity in PSP (PSP 34.4% vs iNPH 16.9%, p = 0.002). Motor dual task revealed a dissociation of gait performance: patients with PSP considerably worsened, but patients with iNPH tended to improve. Conclusion Patients with PSP seem to be more sensitive to dual-task perturbations than patients with iNPH. An increased step width and anisotropy of the effect of dual-task conditions (cognitive vs motor) seem to be good diagnostic tools for iNPH

The cold pressor test in interictal migraine patients - different parasympathetic pupillary response indicates dysbalance of the cranial autonomic nervous system

Background: Data on autonomic nervous system (ANS) activations in migraine patients are quite controversial, with previous studies reporting over-and underactivation of the sympathetic as well as parasympathetic nervous system. In the present study, we explicitly aimed to assess the cranial ANS in migraine patients compared to healthy controls by applying the cold pressor test to a cohort of migraine patients in the interictal phase and measuring the pupillary response. Methods: In this prospective observational study, a strong sympathetic stimulus was applied to 20 patients with episodic migraine in the interictal phase and 20 matched controls without migraine, whereby each participant dipped the left hand into ice-cold (4 degrees C) water for a maximum of 5 min (cold pressor test). At baseline, 2, and 5 min during the cold pressor test, infrared monocular pupillometry was applied to quantify pupil diameter and light reflex parameters. Simultaneously, heart rate and blood pressure were measured by the external brachial RR-method at distinct time intervals to look for at least clinically relevant changes of the cardiovascular ANS. Results: There were no significant differences between the migraine patients and controls at baseline and after 2 min of sympathetic stimulation in all the measured pupillary and cardio-vascular parameters. However, at 5 min, pupillary light reflex (PLR) constriction velocity was significantly higher in migraineurs than in controls (5.59 +/- 0. 73 mm/s vs. 5.16 +/- 0.53 mm/s;unpaired t-test p < 0.05), while both cardiovascular parameters and PLR dilatation velocity were similar in both groups at this time point. Conclusions: Our findings of an increased PLR constriction velocity after sustained sympathetic stimulation in interictal migraine patients suggest an exaggerated parasympathetic response of the cranial ANS. This indicates that brainstem parasympathetic dysregulation might play a significant role in migraine pathophysiology. More dedicated examination of the ANS in migraine patients might be of value for a deeper understanding of its pathophysiology

Bilateral vestibulopathy causes selective deficits in recombining novel routes in real space

The differential impact of complete and incomplete bilateral vestibulopathy (BVP) on spatial orientation, visual exploration, and navigation-induced brain network activations is still under debate. In this study, 14 BVP patients (6 complete, 8 incomplete) and 14 age-matched healthy controls performed a navigation task requiring them to retrace familiar routes and recombine novel routes to find five items in real space. 18F-fluorodeoxyglucose-PET was used to determine navigation-induced brain activations. Participants wore a gaze-controlled, head-fixed camera that recorded their visual exploration behaviour. Patients performed worse, when recombining novel routes (p < 0.001), whereas retracing of familiar routes was normal (p = 0.82). These deficits correlated with the severity of BVP. Patients exhibited higher gait fluctuations, spent less time at crossroads, and used a possible shortcut less often (p < 0.05). The right hippocampus and entorhinal cortex were less active and the bilateral parahippocampal place area more active during navigation in patients. Complete BVP showed reduced activations in the pontine brainstem, anterior thalamus, posterior insular, and retrosplenial cortex compared to incomplete BVP. The navigation-induced brain activation pattern in BVP is compatible with deficits in creating a mental representation of a novel environment. Residual vestibular function allows recruitment of brain areas involved in head direction signalling to support navigation

Additive value of [18F]PI-2620 perfusion imaging in progressive supranuclear palsy and corticobasal syndrome

Purpose: Early after [18F]PI-2620 PET tracer administration, perfusion imaging has potential for regional assessment of neuronal injury in neurodegenerative diseases. This is while standard late-phase [18F]PI-2620 tau-PET is able to discriminate the 4-repeat tauopathies progressive supranuclear palsy and corticobasal syndrome (4RTs) from disease controls and healthy controls. Here, we investigated whether early-phase [18F]PI-2620 PET has an additive value for biomarker based evaluation of 4RTs. Methods: Seventy-eight patients with 4RTs (71 ± 7 years, 39 female), 79 patients with other neurodegenerative diseases (67 ± 12 years, 35 female) and twelve age-matched controls (69 ± 8 years, 8 female) underwent dynamic (0-60 min) [18F]PI-2620 PET imaging. Regional perfusion (0.5-2.5 min p.i.) and tau load (20-40 min p.i.) were measured in 246 predefined brain regions [standardized-uptake-value ratios (SUVr), cerebellar reference]. Regional SUVr were compared between 4RTs and controls by an ANOVA including false-discovery-rate (FDR, p < 0.01) correction. Hypoperfusion in resulting 4RT target regions was evaluated at the patient level in all patients (mean value - 2SD threshold). Additionally, perfusion and tau pattern expression levels were explored regarding their potential discriminatory value of 4RTs against other neurodegenerative disorders, including validation in an independent external dataset (n = 37), and correlated with clinical severity in 4RTs (PSP rating scale, MoCA, activities of daily living). Results: Patients with 4RTs had significant hypoperfusion in 21/246 brain regions, most dominant in thalamus, caudate nucleus, and anterior cingulate cortex, fitting to the topology of the 4RT disease spectrum. However, single region hypoperfusion was not specific regarding the discrimination of patients with 4RTs against patients with other neurodegenerative diseases. In contrast, perfusion pattern expression showed promise for discrimination of patients with 4RTs from other neurodegenerative diseases (AUC: 0.850). Discrimination by the combined perfusion-tau pattern expression (AUC: 0.903) exceeded that of the sole tau pattern expression (AUC: 0.864) and the discriminatory power of the combined perfusion-tau pattern expression was replicated in the external dataset (AUC: 0.917). Perfusion but not tau pattern expression was associated with PSP rating scale (R = 0.402; p = 0.0012) and activities of daily living (R = - 0.431; p = 0.0005). Conclusion: [18F]PI-2620 perfusion imaging mirrors known topology of regional hypoperfusion in 4RTs. Single region hypoperfusion is not specific for 4RTs, but perfusion pattern expression may provide an additive value for the discrimination of 4RTs from other neurodegenerative diseases and correlates closer with clinical severity than tau pattern expression